INTEG.
AND
COMP. BIOL., 42:591–599 (2002)
Social Interaction Over Time, Implications for Stress Responsiveness1
CLIFF H. SUMMERS2
Biology and Neuroscience, University of South Dakota, Vermillion, South Dakota 57069
SYNOPSIS. Behavioral interaction during social situations is a continuum of action, response, and reaction.
The temporal nature of social interaction creates a series of stressful situations, such as aggression, displacement from resources, and the variable psychological challenge of adapting to dynamic social hierarchies.
The ebb and flow of neurochemical and endocrine secretions during social stress provide a unique tool for
understanding individualized responses to stress. Each social station is an adaptive response to a stressful
social condition, resulting in unique neuroendocrine and behavioral responses. By examining the temporal
changes of limbic monoamines and plasma glucocorticoids, aspects of mechanisms for adaptation emerge.
The similarity of temporal patterns induced by social stress among fish, reptiles and primates are remarkable. Even different specific coping mechanisms point out the similarity of vertebrate stress responses. The
lizard Anolis carolinensis exhibits a unique sign stimulus generated during social stress by the sympathetic
nervous system that serves as a temporal landmark to distinguish neuroendocrine patterns. During social
interaction dominant males have a shorter latency to eyespot darkening than opponents, inhibiting aggressive
display. Eyespot coloration can be delayed using a serotonin reuptake inhibitor, causing dominant social
status in many animals to be lost. Reversal of social status via serotonergic activation appears to mimic
chronic serotonergic activity. The pattern of eyespot darkening, faster in dominant males, is coincident with
that for serotonergic activity. The fundamental temporal relationship between dominant and subordinate
limbic monoaminergic activity over a continuous course of social interaction appears to be a two-phase
response, temporally specific to brain region, and always faster in dominant individuals.
INTRODUCTION
Anyone reading this has experienced social stress of
one type or another. Human social stresses are very
complex, excessively imbued with emotional content,
and like those of other animals, are quite dynamic temporally. Expression of behavior and physiology stimulated by stressful social interaction is the result of
mechanisms common to most vertebrate groups, which
are temporally resolved. The mechanisms that mediate
the common patterns are not yet completely known,
but evolutionarily conserved contributions from the
hypothalamo-pituitary-adrenocortial (HPA) axis (Selye, 1936; Herbert et al., 1986; Barton and Vijayan,
2002; Wingfield and Kitaysky, 2002), central glucocorticoid receptors (Moore, 2000; Orchinik et al.,
2000; Carruth et al., 2002), central activity of HPArelated neuropeptides such as CRF (Bale et al., 2002;
Glennemeier and Denver, 2002), the autonomic sympathetic and adrenomedullary secretions (Matt et al.,
1997; Korzan et al., 2000a, 2002), and limbic and
brainstem monoaminergic systems have been widely
reported (Yodyingyuad et al., 1985; Winberg and Nilsson, 1993a; Summers and Greenberg, 1995; Winberg
et al., 1997b; Summers et al., 1998). Even invertebrate
taxa have stress responses similar to those discovered
among vertebrate groups (Stefano et al., 2002), and
may employ similar machinery to produce temporally
resolved behavioral modification, such as serotonergic
activity in lobsters (Huber et al., 2001). Common
mechanisms and patterns of expression need not necessarily yield uniform responses, but are potential substrates for evolutionary modification, and the creation
of context and species specific stress responses. Within
species, variation may result from contextual differences related to morphological type (Knapp and
Moore, 1995), seasonal relationship to breeding
(Moore, 1987; Kotrschal et al., 1998; Romero et al.,
1998; Woodley et al., 2000), weather (Breuner and
Hahn, 2000; Romero et al., 2000; Wingfield and Kitaysky, 2002), migration (Romero et al., 1997), captivity (Romero and Wingfield, 1999), and interactions
with other neuroendocrine systems, such as testosterone from the gonadal axis (Sapolsky, 1985; Moore et
al., 1991; Knapp and Moore, 1997). Groups expressing these neuroendocrine stress response characteristics span a broad spectrum of evolutionary adaptation,
and are illustrative of conservation of, and at the same
time, specialization of response. Most of all, generalizable neuroendocrine response patterns, attuned by individualized stress responsiveness, are adaptive. They
produce context specific behavior, a result of specialized timing for species and even individuals.
SOCIAL INTERACTION IS STRESSFUL FOR BOTH
DOMINANT AND SUBORDINATE MALES
Most studies of behavioral and/or neuroendocrine
stress responsiveness during aggressive social interaction have emphasized the dramatic effects measured
in low-ranking or subordinate males, especially following chronic social interaction (Yodyingyuad et al.,
1985; Blanchard et al., 1993; Fuchs et al., 1995; Summers and Greenberg, 1995; Winberg and Lepage,
1998). In contrast, a few investigators have suggested
that primarily the dominant animal is significantly
1 From the Symposium Stress—Is It More Than a Disease? A
Comparative Look at Stress and Adaptation presented at the Annual
Meeting of the Society for Integrative and Comparative Biology, 3–
7 January 2001, at Chicago, Illinois.
2 E-mail: [email protected]
591
592
CLIFF H. SUMMERS
FIG. 1. Aggressive display behavior increases faster and remains
elevated in dominant (solid line) compared with subordinate (dashed
line) males. These data represent combined results from two experiments. Latency to eyespot darkening is significantly shorter in dominant (top dark horizontal bar) than in subordinate (bottom horizontal
bar) males. Reuptake inhibitor (sertraline) given to dominant males,
chronically elevates serotonergic activity and delays eyespot darkening (top dark 1 clear horizontal bars together), and reverses dominant status. Left bar margin represents the shortest measured latency
(5 sec for dominant and 6 sec for subordinate males) to eyespot
darkening; right bar margin represents the mean latency to darkening.
stressed, especially under natural conditions, because
dominant animals must establish and continually defend territories or maintain priority access to scarce
resources (Packer et al., 1995; Creel et al., 1996; Kotrschal et al., 1998). Taken in the appropriate temporal
perspective, it is clear that the stress response of one
individual influences that of the other (Korzan et al.,
2000a, 2002, Fig. 1). Social interaction is a potent
stressor, and males exposed to persistent subordination
have been demonstrated to have chronically elevated
glucocorticoid concentrations (Yodyingyuad et al.,
1985; Blanchard et al., 1993; Höglund et al., 2000;
Øverli et al., 1999; Winberg and Lepage, 1998) and
chronically elevated serotonergic activity (Summers
and Greenberg, 1995; Summers et al., 1998), but they
also have a fairly fast response to the social stressor.
Within 10 min after beginning aggressive social interaction, subordinate male Anolis carolinensis have elevated serotonergic activity (Korzan et al., 2000b,
2001; Summers et al., 2002), elevated plasma catecholamines (Korzan et al., 2000a, 2002) and elevated
plasma corticosterone concentrations (Summers et al.,
2002). Male A. carolinensis that acquire dominance
during an aggressive social contest also have rapidly
activated serotonergic, sympathetic and HPA systems
(Fig. 2). Similarly in fish, dominant individuals have
increased serotonergic activity and elevated cortisol
levels early during formation of a dominance hierarchy
(Øverli et al., 1999). By one day, both dominant and
subordinate Arctic charr have elevated brainstem 5-HT
synthesis (estimated by precursor tryptophan levels)
and use (measured by elevated catabolite 5-hydroxyindoleacetic acid (5-HIAA) concentrations; Winberg and
Nilsson, 1993b). In the bicolor damselfish (Pomacentrus partitus), both dominant and subordinate males
exhibit a positive correlation between aggression and
serotonergic activity, but the activity was expressed in
different regions of the brain (Winberg et al., 1996).
In dominant males serotonergic activity in hypothalamus is positively correlated with aggressive acts performed. In subordinate males telencephalic 5-HIAA/5HT is positively correlated with aggression received.
Therefore, social interaction is an efficient and physiologically pervasive stressor, rapidly manifest by numerous neural and endocrine systems in both dominant
and subordinate males. Similar early neuroendocrine
responses from dominant and subordinate animals
FIG. 2. Both dominant (solid lines, hatched bar) and subordinate (dashed lines, clear bar) exhibit a robust stress response early during social
atagonism. Notice the similar time course for corticosterone secretion (B, heavier lines) and number of aggressive displays (thin lines with
data points). By ten minutes of social stress plasma corticosterone and catecholamines (not depicted), plus central serotonergic activity (5HIAA/5-HT, bars) are elevated in dominant and subordinate males, even though aggressive behavior has been almost completely inhibited in
subordinate males. Both axes are log scales; smoothed curves for corticosterone concentrations do not signify continuous data. Compare these
data with a more temporally complete depiction of central serotonergic activity in Figures 3 and 4 using the same time scale.
SOCIAL INTERACTION
AND
does not signify that neuroendocrine or behavioral responses remain similar over time.
BEHAVIORAL RESPONSES DIVERGE OVER TIME
In both fish and lizards, the stress response resulting
from social interactions does not produce any behavioral inhibition in dominant individuals, they remain
active and aggressive (Larson and Summers, 2001;
Øverli et al., 1999). However, male A. carolinensis
that become subordinate do begin to show inhibition
of aggressive display and attack, developing over time
(Fig. 1). The initial aggressive reaction in both dominant and subordinate males is rapid (Two-way repeated
measures ANOVA reveal significant time effects, F 5
4.993, P , 0.001) and not significantly different, but
with a tendency toward more quickly aggressive activity in the dominant males (paired t 5 1.78, P .
0.1001). These data suggest two things. The first is
that both males are actively pursuing social dominance, and it is not genetically obvious who the winner
will be. Second, males becoming dominant have the
neuroendocrine machinery to respond more quickly to
social stress. This is visually verified, for the combatants and observers, by darkening of postorbital skin.
Eyespots turn black as early as 5 sec in dominant
males (Fig. 1). The average time for eyespot darkening
in dominant males is 90 sec; but is delayed in subordinate males until 250 (Larson and Summers, 2001) to
300 sec (Summers and Greenberg, 1994). At the same
time subordinate males exhibit eyespot darkening on
average, four to five minutes into the fight, overall
body color of the subordinate male becomes more
brown (Korzan et al., 2002). Dominant males remain
green (Greenberg, 1977, 2002). Furthermore, at five
minutes there appears to be a reassessment of the dynamics of the interaction, because there is a significant
dip (Duncan’s multiple range comparisons, P , 0.04)
in combined aggressive activity for both dominant and
subordinate males aggressive activity. Also by five
minutes, the aggressive activity among subordinate
males is all but significantly (paired t 5 1.92, P ,
0.0785) inhibited compared to dominant males (Fig.
1). The distinction between more aggressive dominant
males and less aggressive subordinate males becomes
statistically significant (Two-way repeated measures
ANOVA reveal significant effects of social status, F
5 15.221, P , 0.002; at 8 min paired t 5 3.82, P ,
0.0025) by eight minutes (Fig. 1).
Like Anolis, some fish species are also chronically
darkened under prolonged social subordination (Höglund et al., 2000). Behavioral and chromatic differences between dominant and subordinate males overlie
differences in neural and endocrine homeostasis
(Greenberg, 2002; Fig. 1). In certain extreme cases,
where there is no avenue for escape, male A. carolinensis may die from social stress within 24 hr, however many pairs coexist for a month or more. Among
males paired for one month, about half the subordinate
animals died, even though cover was provided to allow
them to avoid social interaction (Summers and Green-
STRESS RESPONSIVENESS
593
berg, 1994). Anoles have a socially and physiologically plastic mechanism for limiting social aggression,
darkening of the postorbital skin, or eyespots (Korzan
et al., 2000a, b, 2001, 2002). Eyespots act as a sign
stimulus to inhibit aggressive display, and appear faster in dominant males. However, if chronic 5-HT is
applied pharmacologically to dominant males by the
reuptake inhibitor sertraline, eyespot latency is delayed
(Fig. 1) and many dominant males become subordinate
males (Larson and Summers, 2001). Chronic 5-HT
availability may lead to persistent HPA secretions, as
5-HT contributes to ACTH and corticosterone secretion (Abe and Hiroshige, 1974; Winberg et al., 1997a).
One of the possible factors contributing to the demise
of this subset of persistently subordinate animals is
chronically elevated glucocorticoids (Greenberg et al.,
1984b).
GLUCOCORTICOID RESPONSES DIFFER TEMPORALLY
Although a rapid social activation of the HPA axis
produces elevated plasma cortisol concentrations in
dominant fish (Øverli et al., 1999), following prolonged social interaction in secure social hierarchies,
cortisol levels in dominant fish are usually low (Höglund et al., 2000; Øverli et al., 1999; Winberg and
Lepage, 1998). This is in contrast with chronically
high plasma cortisol in subordinate fish (Elofsson et
al., 2000; Höglund et al., 2000; Øverli et al., 1999;
Winberg and Lepage, 1998). In A. carolinensis, the
patterns of corticosterone secretion also appears to be
different for acute and chronic social stress (Fig. 2).
Although in both dominant and subordinate males
plasma corticosterone is elevated early (by 10 min)
during social stress and diminishes by 20 min, thereafter only subordinate males have re-elevated plasma
corticosterone (Greenberg et al., 1984b; Summers et
al., 2002). After three weeks cohabitation and presumably some social stress, corticosterone concentrations
appear to have remained chronically elevated in subordinate, but not dominant, males (Greenberg et al.,
1984b). Subordinate fish (Winberg and Lepage, 1998)
and subordinate monkeys (Yodyingyuad et al., 1985)
also have chronically elevated glucocorticoid levels,
measured at from a week to a month of social interaction. Hormonal responses to stress have been demonstrated to vary dependent on social status in many
types of vertebrates, encompassing fishes (Winberg
and Lepage, 1998; Elofsson et al., 2000), reptiles
(Summers et al., 2002), birds (Kotrschal et al., 1998;
Wingfield and Kitaysky, 2002) and mammals (Blanchard et al., 1993; McKittrick et al., 1995) including
primates (Sapolsky, 1983; Yodyingyuad et al., 1985).
Temporal resolution of the glucocorticoid response
suggests a dynamic secretory pattern for corticosterone
due to social stress in A. carolinensis, with acute elevation common to both dominant and subordinate
males (Fig. 2), and chronic elevation measured in subordinate animals (Summers et al., 2002).
594
CLIFF H. SUMMERS
GLUCOCORTICOID RESPONSES MAY OR MAY NOT
REFLECT ALL STAGES OF SOCIAL STRESS
Peripheral responses, especially corticosterone or
cortisol, to social stress and aggression are the most
widely chosen measures of stress responsiveness
(Christian, 1963, 1968; Sapolsky, 1983; Winberg and
Lepage, 1998; Breuner and Hahn, 2000; Barton and
Vijayan, 2002; Carruth et al., 2002; Wingfield and Kitaysky, 2002). Although most investigators report a
fairly rapid and robust glucocorticoid response to
stress (Moore et al., 1991; Moore, 2000; Orchinik et
al., 2000; Woodley et al., 2000), some have not
(Moore, 1987; Knapp and Moore, 1995). There have
been recent studies suggesting that cortisol concentrations may not reflect human reactivity to stressful conditions in real life situations at all (Pollard, 1995). Plus
there are some fish species whose glucocorticoid response is extremely muted and slow, although present
(Barton and Vijayan, 2002). There are a number of
reports that suggest that specific neuroendocrine responses are dependent on the specific stressor (Luo et
al., 1994; Pacak et al., 1995, 1998; Romero and Sapolsky, 1996; Dhabar et al., 1997). Many investigators
currently believe after substantial results have been
collected from clinical, laboratory and field studies,
that neuroendocrine stress responses are context dependent (Breuner and Hahn, 2000; Hayes, 2000; Carr
et al., 2002; Carr and Summers, 2002; Greenberg,
2002; Greenberg et al., 2002; Wingfield and Kitaysky,
2002). However, specificity of response dependent on
context and type of stressor may represent plasticity
or flexibility of neuroendocrine stress machinery common to all stressors, rather than multiple systems set
up for each stressor and each context. Plasticity in the
timing of common responses is a reasonable mechanism to give flexibility that results in differential responses seen for various stressors and contexts. An
example of flexibility of neuroendocrine response may
be found in the lizard A. carolinensis (Korzan et al.,
2000a, b). With respect to corticosterone secretion,
two reports by Greenberg and colleagues left those investigators wondering whether social stress was
enough to stimulate the HPA axis (Greenberg et al.,
1984b; Greenberg and Crews, 1990). The first study
showed a substantial increase in plasma corticosterone
induced by social stress in subordinate males (Greenberg et al., 1984b). A more recent study, with a sampling regimen at 3 different and earlier time periods,
did not produce any statistically significant elevations
in corticosterone (Greenberg and Crews, 1990). Very
recent work suggests that the corticosteroid response
in A. carolinensis is extremely labile (Summers et al.,
2002), implying that perhaps both earlier studies were
accurate. Trying to infer a pattern of glucocorticoid
response in A. carolinensis from an amalgam of these
three studies, suggests a rapid increase in corticosterone secretion by ten minutes in both dominant and
subordinate males in response to acute stress and aggression (Summers et al., 2002). This early response
is very nicely correlated with an easily identifiable
stressor. Very quickly, both males reduce corticosterone secretion to baseline levels. In the period that
follows, from 40 min through a week or so, ensuing
social interactions may stimulate elevated glucocorticoid responses from both dominant and subordinate
males, but they are more likely and longer lasting in
subordinate males (Sapolsky, 1983, 1989). During this
time period elevated corticosterone was measured in
subordinate males at 40 min (Summers et al., 2002),
but not at one hour, one day, or one week (Greenberg
and Crews, 1990) although there was a trend toward
increases in both dominant and subordinate males. Although social aggression decreases during that period,
the persistent nature of social stress for subordinate
individuals may eventually lead to chronically elevated
corticosterone, as was measured by Greenberg et al.
at three weeks (1984b). Therefore, although there appear to be clearly defined acute and chronic phases of
HPA axis activity, there are periods when sampling
may not result in elevated glucocorticoids. It would be
a mistake to suggest that social stress is absent during
those periods when corticosteroid concentrations are
not elevated.
SOCIAL STRESS IS BIPHASIC
Descriptions of stress responsiveness from the very
beginning (Selye, 1936, 1937) have contrasted neuroendocrine secretion as acute versus chronic. Chronic
stress responses are often viewed as maladaptive or
pathological (Carr and Summers, 2002), and acute
stress responses are more likely to be seen as adaptive,
if not beneficial. However, all of the temporal manifestations of the stress response have important and
adaptive behavioral consequences, which also influence the neuroendocrine machinery of the stress response (Summers, 2001).
Long-term temporal resolution and continuity of behavioral displays have not been quantified for Anolis,
but it is clear that during social interaction aggression
declines with time (Fig. 1). A look at display frequency during the first ten minutes of social interaction
suggests a temporally bimodal distribution of aggressive acts for dominant (aggressive) males and also for
subordinate (less aggressive) males. A significant decline in aggression at five minutes, suggests a period
of reassessment, after which aggressive display by
subordinate males decline.
Neuroendocrine responses to social stress also appear to be biphasic during the early and later phases
of social interaction. Corticosterone concentrations in
subordinate males peak twice during the first hour
(Fig. 2), and then perhaps again much later (Greenberg
et al., 1984b). The glucocorticoid response appears to
be regulated, at least in part by central serotonergic
activity (Abe and Hiroshige, 1974; Winberg et al.,
1997a). In concert with HPA reactions, serotonergic
activity of limbic structures increases by ten minutes
in both dominant and subordinate males, followed by
a secondary escalation in both, peaking at various
SOCIAL INTERACTION
AND
STRESS RESPONSIVENESS
595
FIG. 3. Social stress-induced secondary phase (II) increase in serotonergic activity (estimated by 5-HIAA/5-HT) is substantially delayed in
medial amygdala 1 striatum (taken together) of subordinate (IIsub) compared with dominant (IIdom) male Anolis carolinensis (Summers et al.,
1998, 2002). The initial phase (I) of serotonergic activity in response to social stress is early in both dominant and suborinate males. Both
axes are log scales; smoothed curves do not signify continuous data. The difference in time between serotonergic activity in dominant and
subordinate males is indicated by an arrow.
times later during the period of social stress (Summers
et al., 2002). It is the timing of the secondary increase
in neuroendocrine activity that appears to be one way
to distinguish dominant and subordinate social status.
SEROTONERGIC RESPONSE IS SIMILAR FOR DOMINANT
AND SUBORDINATE MALES, BUT TEMPORALLY OFFSET
There are two characteristics of serotonergic activity
induced by social stress that are similar in dominant
and subordinate males. A rapid increase in central serotonergic activity occurs in any male, and perhaps
any female (Summers et al., 1997), A. carolinensis that
engages in aggressive social interaction (Summers et
al., 2002). How rapid is still unknown, but before 25
sec is a reasonable guess, as physical stress in A. carolinensis (Emerson et al., 2000), and social stress in
Sceloporus jarrovi (Matter et al., 1998) enhance 5HIAA/5-HT levels in this time frame (Summers,
2001). It seems likely that this early serotonergic activity, along with elevated plasma corticosterone, are
responses to stress associated with novel aggression.
During this early response period, through about ten
minutes, dopaminergic and noradrenergic systems are
also affected, but it is the serotonergic system activity
that is most closely correlated with social and other
stresses (Winberg and Nilsson, 1993a). Dominant and
subordinate male serotonergic response to aggressive
social interaction also similarly produce a secondary
period of enhanced activity (Summers et al., 2002).
The secondary serotonergic responses are not temporally similar, but offset.
Regardless of limbic region investigated, the secondary phase of enhanced serotonergic activity in subordinate male A. carolinensis is delayed compared
with dominant males (Fig. 3). It is not surprising that
monoaminergic activity is different in limbic regions
based on social status, as prolonged subordination
stress induces morphological changes in nucleus
(Fuchs et al., 1995) and dendritic arbors (Margariños
et al., 1996) of hippocampal pyramidal cells, and also
decreases binding of 5-HT transporters (McKittrick et
al., 2000). In hippocampus (medial cortex) and nucleus accumbens dominant male A. carolinensis have secondary serotonergic peaks by 40 min of social interaction (Summers et al., 2002). Subordinate males do
not have a second period of enhanced serotonergic activity until an hour in those regions, and peak activity
is delayed until one week in medial amygdala-striatum.
DIFFERENT, BUT INTERACTIVE REGIONS OF THE BRAIN
APPEAR TO REGULATE SHORT-TERM AND LONG-TERM
STRESS
The delay in enhanced serotonergic activity in the
amygdalo-striatal region (posterior dorsal ventricular
ridge plus paleostriatum; Greenberg, 1982; Bruce and
Neary, 1995) is expressed in both dominant and subordinate male Anolis (Summers et al., 2002). The difference is that for dominant males the shift in peak
activity is from 40 min for hippocampus or accumbens
to an hour in medial amygdala-striatum, and in subordinate males the delay in serotonergic activity is
much longer (Fig. 4). Serotonergic activity in mammalian amygdala stimulates the HPA axis (Feldman et
al., 2000) via circuitry through the bed nucleus of the
stria terminalis shared with the hippocampus (Herman
and Cullinan, 1997; Herman and Ziegler, 2002). The
hippocampus is an important site for negative feedback and inhibition of the HPA endocrine stress response (Sapolsky et al., 1984). Centrally and peripherally applied corticosterone stimulates serotonergic
activity in the hippocampal cortex of A. carolinensis
596
CLIFF H. SUMMERS
FIG. 4. Social stress-induced secondary phase (II) increase in serotonergic activity (estimated by 5-HIAA/5-HT) is substantially delayed in
medial amygdala 1 striatum (taken together; IImA/Str) compared with hippocampus (IIhip) of subordinate male Anolis carolinensis (Summers et
al., 1998, 2002). The initial phase (I) of serotonergic activity in response to social stress is early in both hippocampus and amygdala 1
striatum. Both axes are log scales; curves smoothed discontinuous data. The difference in time between serotonergic activity in the two brain
regions is indicated by an arrow.
(Summers et al., 2000; Summers, 2001), so negative
feedback may include a serotonergic component.
As hippocampal serotonergic activity occurs sooner,
along with hippocampus being inhibitory for the HPA
endocrine response, and because dominant male A.
carolinensis have the most rapid hippocampal serotonergic response coupled with a lack of chronically elevated plasma corticosterone (Greenberg et al., 1984b;
Greenberg and Crews, 1990), the hippocampus seems
well suited to regulate short-term stress responses. On
the other hand, serotonergic activity in amygdala stimulates HPA secretion (Feldman et al., 2000), serotonergic activity in anoline medial amygdala and striatum are delayed, and delayed in subordinate males to
reasonably coincide with elevated corticosterone late
(three weeks) in social cohabitation (Greenberg et al.,
1984b). The evidence suggests that the processing of
stress-related information occurs in a distributed fashion, with short-term regulation and inhibition of HPA
activity controlled by hippocampus, and longer-term
stimulation of HPA secretion associated with social
subordination and the attendant behavior regulated by
amygdala. The medial amygdala and ventral striatum
are regions that regulate aggression and species specific social behavior in Anolis (Greenberg et al., 1979,
1984a, 1988; Greenberg, 1983). In this cooperative
regulation scheme, these regions must relay current
conditions between them, and there must be a mechanism to convert short-term reactions that facilitate
more aggression into longer-term responsiveness that
includes submissive behavior for subordinate animals.
FASTER NEUROENDOCRINE RESPONSES IN MALES MAY
PERMIT BEHAVIORAL ADAPTATION FOR DOMINANT
SOCIAL ROLES
As no animal is born dominant, the neuroendocrine
machinery necessary for producing stress responses
and the appropriate behavior for dominant status must
be acquired. In addition, any individual may encounter
an antagonist of greater or lesser social experience,
ability and status each time an interaction takes place.
Variation in neuroendocrine responsiveness appears to
emanate, at least in part, from different social experience (Sapolsky, 1985; Knapp and Moore, 1996).
Therefore, the neuroendocrine machinery necessary to
produce appropriate behavioral responses must be easily modifiable (Summers, 2001). A plausible mechanism for both ontogenetic development and flexibility
of the appropriate neuroendocrine machinery to handle
the quick and variable responses necessary for varying
social contexts, is simply the speed of the neuroendocrine stress response. A dominant male must always
be alert and ready, and quicker to show aggressive
intent, assess his opponent, and limit his opponent’s
aggression if he is to be/remain dominant and to limit
his own stress response (Summers, 2001). Rapidly
limiting the stress response via the hippocampus presents the dominant male with behavioral opportunities
uninhibited by chronically elevated corticosterone or
5-HT. Alertness, aggressive display, aggression, feeding and locomotion are all inhibited by 5-HT or corticosterone during social stress (Winberg et al., 1993a,
b; Larson and Summers, 2001).
CERTAIN SOCIAL INTERACTIONS MAY RESULT
NEUROENDOCRINE RESPONSES
IN
FASTER
While neuroendocrine secretory products such as
corticosterone and 5-HT influence behavior (Larson
and Summers, 2001), behavior and social sign stimuli
also influence neuroendocrine output (Korzan et al.,
2000a, b, 2001, 2002). Specifically for Anolis, viewing
aggression stimulates more aggressive activity (Yang
et al., 2001), but it also influences central and plasma
SOCIAL INTERACTION
AND
monoamine activity (Korzan et al., 2000a, b, 2001,
2002). In addition, eyespots appear to specifically
stimulate the dopaminergic centers substantia nigra
and ventral tegmental area (Korzan et al., 2001). When
measured together nigral and tegmental dopaminergic,
serotonergic and noradrenergic activity is elevated
when a male views a mirrored reflection of himself as
an opponent with darkened eyespots. The implication
is that behavioral events, perhaps along with a genetic
predisposition, are a part of the means by which the
necessary neuroendocrine machinery is accrued during
development of dominant characteristics and capacities, and during acquisition of dominance itself. It is
unknown which kinds of experience may result in
shorter latency to neuroendocrine response to stressors
characteristic of dominant animals, but likely candidates include winning aggressive interactions, interactions with opponents without darkened eyespots,
winning competition for food and mates, and successful copulations.
SUMMARY
Social interaction is stressful for both dominant and
subordinate males. However, the temporal resolution
of neuroendocrine stress responses depends on social
status, and appears to be an accurate measure of social
status. Therefore, behavioral responses develop differently between dominant and subordinate males over
time. Peripheral responses to stressful social stimuli,
like glucocorticoids, may be attuned to social status at
some times during social interaction, but do not always
reflect the presence of social stress. Social stress is
temporally biphasic, with bimodal behavioral and neuroendocrine responses. Serotonergic activity in response to social stress is attuned to temporal changes
in behavior and status. That is, serotonergic activity is
similar for dominant and subordinate males, but temporally offset. To regulate the temporally integrated
and interactive set of neuroendocrine changes associated with social stress, different, but interactive regions
of the brain appear to govern short-term and long-term
stress. Faster neuroendocrine responses in males may
permit behavioral adaptation for dominant social roles.
Certain social interactions may result in faster neuroendocrine responses.
ACKNOWLEDGMENTS
The symposium and resulting published works were
funded by NIH grant R13 MH62670, NSF grant IBN
#0100532, the Center for Biomedical Research Excellence (CoBRE) at the University of South Dakota on
Neural Mechanisms of Adaptive Behavior, South Dakota EPSCoR, and the USD Office of Research. The
data presented here represents contributions from numerous students, colleagues and collaborators, including Aaron Emerson, Neil Greenberg, Wayne J. Korzan,
Earl T. Larson, Christopher A. Lowry, John M. Matter,
Jennifer McKay, Michael C. Moore, Aaron Prestbo,
Kenneth J. Renner, Patrick J. Ronan, Tangi R. Summers, Gary R. Ten Eyck and Sarah Woodley. Work
STRESS RESPONSIVENESS
597
presented here was supported by NIH grants P20
RR15567 & NICHD-1-T32-HDO 7303-01A1, NSF
grants IBN-9596009, OSR-9108773 & 9452894 &
NSF EPSCoR Research Fellowship, HHMI grant
71195-539501, Nelson Foundation fellowship and
grant, and Sigma Xi Grant-in-Aid of Research.
REFERENCES
Abe, K. and T. Hiroshige. 1974. Changes in plasma corticosterone
and hypothalamic CRF levels following intraventricular injection or drug-induced changes of brain biogenic amines in the
rat. Neuroendocrinology 14:195–211.
Bale, T., M. H. Perrin, K.-F. Lee, K. Lewis, J. Vaughan, and W. Vale.
2002. The role of corticotropin-releasing factor receptors in
stress and anxiety. Int. Comp. Biol. 42:552–555.
Ball, G. F. and J. Balthazart. 2001. Ethological concepts revisited:
Immediate early gene induction in response to sexual stimuli in
birds. Brain Behav. Evol. 57:252–270.
Barton, B. and M. M. Vijayan. 2002. Stress in fishes: A diversity of
responses with particular reference to stress-induced changes in
corticosteroids. Int. Comp. Biol. 42:517–525.
Blanchard, D. C., R. R. Sakai, B. McEwen, S. M. Weiss, and R. J.
Blanchard. 1993. Subordination stress: Behavioral, brain, and
neuroendocrine correlates. Behav. Brain Res. 58:113–121.
Breuner, C. W. and T. P. Hahn. 2000. Corticosterone and inclement
weather: Mechanisms underlying adaptive behavioral responses
in mountain birds. Amer. Zool. 40:954.
Bruce, L. L. and T. J. Neary. 1995. The limbic system of tetrapods:
A comparative analysis of cortical and amygdalar populations.
Brain Behav. Evol. 46:224–234.
Carr, J. A., C. L. Brown, R. Mansouri, and S. Venkatesan. 2002.
Stress, neuropeptides and feeding behavior: A comparative perspective. Int. Comp. Biol. 42:582–590.
Carr, J. A. and C. H. Summers. 2002. Is stress more than a disease?
A comparative look at stress and adaptation. Int. Comp. Biol.
42:505–507.
Carruth, L. L., R. E. Jones, and D. O. Norris. 2002. Stress and pacific
salmon: A new look at the role of cortisol in olfaction and
home-stream migration. Int. Comp. Biol. 42:574–581.
Christian, J. J. 1963. Interrelated social and endocrine factors in
populations of rodents. Proc. XVI Int. Cong. Zool. 3:8–13.
Christian, J. J. 1968. The potential role of the adrenal cortex as
affected by social rank and population density on experimental
epidemics. Am. J. Epidemiol. 87:255–264.
Creel, S., N. M. Creel, and S. L. Monfort. 1996. Social stress and
dominance. Nature 379:212.
Dhabhar, F. S., B. S. McEwen, and R. L. Spencer. 1997. Adaptation
to prolonged or repeated stress–comparison between rat strains
showing intrinsic differences in reactivity to acute stress. Neuroendocrinology 65:360–368.
Elofsson, U. O., I. Mayer, B. Damsgard, and S. Winberg. 2000.
Intermale competition in sexually mature arctic charr: Effects
on brain monoamines, endocrine stress responses, sex hormone
levels, and behavior. Gen. Comp Endocrinol. 118:450–460.
Emerson, A. J., D. P. Kappenman, P. J. Ronan, K. J. Renner, and C.
H. Summers. 2000. Stress induces rapid changes in serotonergic
activity: Restraint and exertion. Behav. Brain Res. 111:83–92.
Feldman, S., M. E. Newman, and J. Weidenfeld. 2000. Effects of
adrenergic and serotonergic agonists in the amygdala on the
hypothalamo-pituitary-adrenocortical axis. Brain Res. Bull. 52:
531–536.
Fuchs, E., H. Uno, and G. Flügge. 1995. Chronic psychosocial stress
induces morphological alterations in hippocampal pyramidal
neurons of the tree shrew. Brain Res. 673:275–282.
Glennemeier, K. A. and R. J. Denver. 2002. Developmental changes
in interrenal responsiveness in anuran amphibians. Int. Comp.
Biol. 42:565–573.
Greenberg, N. 1977. A neuroethological study of display behavior
in the lizard, Anolis carolinensis (Reptilia, Lacertilia, Iguanidae). Amer. Zool. 17:191–201.
598
CLIFF H. SUMMERS
Greenberg, N. 1982. A forebrain atlas and stereotaxic technique for
the lizard, Anolis carolinensis. J. Morphol. 174:217–236.
Greenberg, N. 1983. Central and autonomic aspects of aggression
and dominance in reptiles. In J. P. Ewert, R. R. Capranica, and
D. J. Ingle (eds.), Advances in vertebrate neuroethology, pp.
1135–1143. Plenum, New York.
Greenberg, N. 2002. Causes and consequences of the stress response
in reptiles. Int. Comp. Biol. 42:526–540.
Greenberg, N., J. A. Carr, and C. H. Summers. 2002. Causes and
consequences of the stress response. Int. Comp. Biol. 42:508–
516.
Greenberg, N., T. Chen, and D. Crews. 1984b. Social status, gonadal
state, and the adrenal stress response in the lizard, Anolis carolinensis. Horm. Behav. 18:1–11.
Greenberg, N. and D. Crews. 1990. Endocrine and behavioral responses to aggression and social dominance in the green anole
lizard, Anolis carolinensis. Gen. Comp-Endocrinol. 77:246–
255.
Greenberg, N., E. Font, and R. C. Switzer. 1988. The reptilian striatum revisited: Studies on Anolis lizards. In W. K. Schwerdtfeger and W. J. A. J. Smeets (eds.), The forebrain of reptiles,
pp.162–177. Karger, Basel.
Greenberg, N., P. D. MacLean, and J. L. Ferguson. 1979. Role of
the paleostriatum in species-typical display behavior of the lizard (Anolis carolinensis). Brain Res. 172:229–241.
Greenberg, N., M. Scott, and D. Crews. 1984a. Role of the amygdala
in the reproductive and aggressive behavior of the lizard, Anolis
carolinensis. Physiol. Behav. 32:147–151.
Hadley, M. E. and J. M. Goldman. 1969. Physiological color changes in reptiles. Amer. Zool. 9:489–504.
Hayes, T. 2000. Evolutionary developmental endocrinology and behavioral ecology: An integrative approach to understanding the
stress response in western toads (Bufo boreas). Amer. Zool. 40:
1049–1050.
Herbert, J., E. B. Keverne, and U. Yodyingyuad. 1986. Modulation
by social status of the relationship between cerebrospinal fluid
and serum cortisol levels in male talapoin monkeys. Neuroendocrinology 42:436–442.
Herman, J. P. and W. E. Cullinan. 1997. Neurocircuitry of stress:
Central control of the hypothalamo-pituitary-adrenocortical
axis. Trends Neurosci. 20:78–84.
Herman, J. P. and D. R. Ziegler. 2002. Neurocircuitry of stress integration: Anatomical pathways regulating the hypothalamo-pituitary-adrenocortical axis of the rat. Int. Comp. Biol. 42:541–
551.
Höglund, E., P. H. Balm, and S. Winberg. 2000. Skin darkening, a
potential social signal in subordinate arctic charr (Salvelinus
alpinus): The regulatory role of brain monoamines and proopiomelanocortin-derived peptides. J. Exp. Biol. 203:1711–
1721.
Huber, R., J. B. Panksepp, and Z. Yue. 2001. Dynamic interactions
of behavior and amine neurochemistry during acquisition and
maintenance of social rank in crayfish. Brain Behav. Evol. 57:
271–282.
Knapp, R. and M. C. Moore. 1995. Hormonal responses to aggression vary in different types of agonistic encounters in male tree
lizards, Urosaurus ornatus. Horm. Behav. 29:85–105.
Knapp, R. and M. C. Moore. 1996. Male morphs in tree lizards,
Urosaurus ornatus, have different delayed hormonal responses
to aggressive encounters. Anim. Behav. 52:1045–1055.
Knapp, R. and M. C. Moore. 1997. Male morphs in tree lizards have
different testosterone responses to elevated levels of corticosterone. Gen. Comp. Endocrinol. 107:273–279.
Korzan, W. J., T. R. Summers, P. J. Ronan, and C. H. Summers.
2000a. Visible sympathetic activity as a social signal in Anolis
carolinensis: Changes in aggression and plasma catecholamines. Horm. Behav. 38:193–199.
Korzan, W. J., T. R. Summers, P. J. Ronan, K. J. Renner, and C. H.
Summers. 2001. The role of monoaminergic perikarya during
aggression and sympathetic social signaling. Brain Behav. Evol.
57:317–327.
Korzan, W. J., T. R. Summers, and C. H. Summers. 2000b. Monoaminergic activities of limbic regions are elevated during ag-
gression: Influence of sympathetic social signaling. Brain Res.
870:170–178.
Korzan, W. J., T. R. Summers, and C. H. Summers. 2002. Manipulation of visual sympathetic sign stimulus modifies social status
and plasma catecholamines. Gen. Comp. Endocrinol. (In press)
Kotrschal, K., K. Hirschenhauser, and E. Möstl. 1998. The relationship between social stress and dominance is seasonal in greylag
geese. Anim. Behav. 55:171–176.
Larson, E. T. and C. H. Summers. 2001. Serotonin reverses dominant
social status. Behav. Brain Res. 121:95–102.
Luo, X., A. Kiss, G. Makara, S. J. Lolait, and G. Aguilera. 1994.
Stress-specific regulation of corticotropin releasing hormone receptor expression in the paraventricular and supraoptic nuclei
of the hypothalamus in the rat. J. Neuroendocrinol. 6:689–696.
Magariños, A. M., B. S. McEwen, G. Flügge, and E. Fuchs. 1996.
Chronic psychosocial stress causes apical dendritic atrophy of
hippocampal CA3 pyramidal neurons in subordinate tree shrews.
J. Neurosci. 16:3534–3540.
Matt, K. S., M. C. Moore, R. Knapp, and I. T. Moore. 1997. Sympathetic mediation of stress and aggressive competition: Plasma
catecholamines in free-living male tree lizards. Physiol. Behav.
61:639–647.
Matter, J. M., P. J. Ronan, and C. H. Summers. 1998. Central monoamines in free-ranging lizards: Differences associated with social roles and territoriality. Brain Behav. Evol. 51:23–32.
McKittrick, C. R., D. C. Blanchard, R. J. Blanchard, B. S. McEwen,
and R. R. Sakai. 1995. Serotonin receptor binding in a colony
model of chronic social stress. Biol. Psychiatry 37:383–393.
McKittrick, C. R., A. M. Magarinos, D. C. Blanchard, R. J. Blanchard, B. S. McEwen, and R. R. Sakai. 2000. Chronic social
stress reduces dendritic arbors in CA3 of hippocampus and decreases binding to serotonin transporter sites. Synapse 36:85–
94.
Moore, F. L. 2000. Ultimate and proximate mechanisms that control
the stress-induced inhibition of reproductive behaviors. Amer.
Zool. 40:1136–1137.
Moore, M. C. 1987. Circulating steroid hormones during rapid aggressive responses of territorial male mountain spiny lizards,
Sceloporus jarrovi. Horm. Behav. 21:511–521.
Moore, M. C., C. W. Thompson, and C. A. Marler. 1991. Reciprocal
changes in corticosterone and testosterone levels following
acute and chronic handling stress in the tree lizard, Urosaurus
ornatus. Gen. Comp. Endocrinol. 81:217–226.
Orchinik, M., C. W. Breuner, P. Gasser, and D. Jennings. 2000. Diversity and plasticity in corticosteroid action. Amer. Zool. 40:
1158–1159.
Øverli, Ø., C. A. Harris, and S. Winberg. 1999. Short-term effects
of fights for social dominance and the establishment of dominant-subordinate relationships on brain monoamines and cortisol in rainbow trout. Brain Behav. Evol. 54:263–275.
Pacak, K., M. Palkovits, R. Kvetnansky, G. Yadid, I. J. Kopin, and
D. S. Goldstein. 1995. Effects of various stressors on in vivo
norepinephrine release in the hypothalamic paraventricular nucleus and on the pituitary-adrenocortical axis. Ann. N.Y. Acad.
Sci. 771:115–130.
Pacak, K., M. Palkovits, G. Yadid, R. Kvetnansky, I. J. Kopin, and
D. S. Goldstein. 1998. Heterogeneous neurochemical responses
to different stressors: A test of Selye’s doctrine of nonspecificity. Am. J. Physiol. 275:R1247–R1255.
Packer, C., D. A. Collins, A. Sindimwo, and J. Goodall. 1995. Reproductive constraints on aggressive competition in female baboons. Nature 373:60–63.
Pollard, T. M. 1995. Use of cortisol as a stress marker: Practical and
theoretical problems. Am. J. Human Biol. 7:265–274.
Romero, L. M. and R. M. Sapolsky. 1996. Patterns of ACTH secretagog secretion in response to psychological stimuli. J. Neuroendocrinol. 8:243–258.
Romero, L. M., M. Ramenofsky, and J. C. Wingfield. 1997. Season
and migration alters the corticosterone response to capture and
handling in an Arctic migrant, the white-crowned sparrow (Zonotrichia leucophrys gambelii). Comp. Biochem. Physiol. C.
116:171–177.
Romero, L. M., K. K. Soma, and J. C. Wingfield. 1998. Hypotha-
SOCIAL INTERACTION
AND
lamic-pituitary-adrenal axis changes allow seasonal modulation
of corticosterone in a bird. Am. J. Physiol. 274:R1338–R1344.
Romero, L. M. and J. C. Wingfield. 1999. Alterations in hypothalamic-pituitary-adrenal function associated with captivity in
Gambel’s white-crowned sparrows (Zonotrichia leucophrys
gambelii). Comp. Biochem. Physiol. B 122:13–20.
Romero, L. M., J. M. Reed, and J. C. Wingfield. 2000. Effects of
weather on corticosterone responses in wild free-living passerine birds. Gen. Comp. Endocrinol. 118:113–122.
Sapolsky, R. 1983. Individual differences in cortisol secretory patterns in the wild baboon: Role of negative feedback sensitivity.
Endocrinology 113:2263–2267.
Sapolsky, R. 1985. Stress-induced suppression of testicular function
in the wild baboon: Role of glucocorticoids. Endocrinology
116:2273–2278.
Sapolsky, R. 1989. Hypercortisolism among socially subordinate
wild baboons orginates at the CNS level. Arch. Gen. Psychiatry
46:1047–1051.
Sapolsky, R., L. C. Krey, and B. McEwen. 1984. Glucocorticoidsensitive hippocampal neurons are involved in terminating the
adrenocortical stress response. Proc. Natl. Acad. Sci. U.S.A. 81:
6174–6177.
Selye, H. 1936. A syndrome produced by diverse nocuous agents.
Nature 138:32.
Selye, H. 1937. Studies on adaptation. Endocrinology 21:169–188.
Stefano, G. B., P. Cadet, W. Zhu, C. M. Rialas, K. Mantione, D.
Benz, R. Fuentes, F. Casares, G. L. Fricchione, Z. Fulop, and
B. Slingsby. 2002. The blueprint for stress can be found in
invertebrates. Neuroendocrinol. Lett. 23:85–93.
Summers, C. H. 2001. Mechanisms for quick and variable responses.
Brain Behav. Evol. 57:283–292.
Summers, C. H. and N. Greenberg. 1994. Somatic correlates of adrenergic activity during aggression in the lizard, Anolis carolinensis. Horm. Behav. 28:29–40.
Summers, C. H. and N. Greenberg. 1995. Activation of central biogenic amines following aggressive interaction in male lizards,
Anolis carolinensis. Brain Behav. Evol. 45:339–349.
Summers, C. H., E. T. Larson, T. R. Summers, K. J. Renner, and N.
Greenberg. 1998. Regional and temporal separation of serotonergic activity mediating social stress. Neuroscience 87:489–
496.
Summers, C. H., E. T. Larson, P. J. Ronan, P. M. Hofmann, A. J.
Emerson, and K. J. Renner. 2000. Serotonergic responses to
corticosterone and testosterone in the limbic system. Gen.
Comp. Endocrinol. 117:151–159.
Summers, C. H., T. R. Summers, M. C. Moore, W. J. Korzan, S. K.
Woodley, P. J. Ronan, E. Höglund, M. Watt, and N. Greenberg.
2002. Temporal patterns of limbic monoamine and plasma cor-
STRESS RESPONSIVENESS
599
ticosterone response during social stress. Neuroscience (In
press)
Summers, T. R., A. L. Hunter, and C. H. Summers. 1997. Female
social reproductive roles affect central monoamines. Brain Res.
767:272–278.
Winberg, S. and G. E. Nilsson. 1993b. Time course of changes in
brain serotonergic activity and brain tryptophan levels in dominant and subordinate juvenile arctic charr. J. Exp. Biol. 179:
181–195.
Winberg, S., C. G. Carter, I. D. McCarthy, Z.-Y. He, G. E. Nilsson,
and D. F. Houlihan. 1993a. Feeding rank and brain serotonergic
activity in rainbow trout Oncorhynchus mykiss. J. Exp. Biol.
179:197–211.
Winberg, S. and O. Lepage. 1998. Elevation of brain 5-HT activity,
POMC expression, and plasma cortisol in socially subordinate
rainbow trout. Am. J. Physiol. 274:R645–R654.
Winberg, S., A. A. Myrberg, Jr., and G. E. Nilsson. 1996. Agonistic
interactions affect brain serotonergic activity in an acanthopterygiian fish: The bicolor damselfish (Pomacentrus partitus).
Brain Behav. Evol. 48:213–220.
Winberg, S. and G. E. Nilsson. 1993a. Roles of brain monoamine
transmitters in agonistic behaviour and stress reactions, with
particular reference to fish. Comp. Biochem. Physiol. 106C:
597–614.
Winberg, S., G. E. Nilsson, B. M. Spruijt, and U. Höglund. 1993b.
Spontaneous locomotor activity in Arctic charr measured by a
computerized imaging technique: Role of brain serotonergic activity. J. Exp. Biol. 179:213–232.
Winberg, S., A. Nilsson, P. Hylland, V. Soderstom, and G. E. Nilsson. 1997a. Serotonin as a regulator of hypothalamic-pituitaryinterrenal activity in teleost fish. Neurosci. Lett. 230:113–116.
Winberg, S., Y. Winberg, and R. D. Fernald. 1997b. Effect of social
rank on brain monoaminergic activity in a cichlid fish. Brain
Behav. Evol. 49:230–236.
Wingfield, J. C. and A. Kitaysky. 2002. Endocrine responses to unpredictable environmental events: Stress or anti-stress hormones? Int. Comp. Biol. 42:600–609.
Woodley, S. K., K. S. Matt, and M. C. Moore. 2000. Neuroendocrine
responses in free-living female and male lizards after aggressive
interactions. Physiol. Behav. 71:373–381.
Yang, E.-J., S. M. Phelps, D. Crews, and W. Wilczynski. 2001. The
effects of social experience on aggressive behavior in the green
anole lizard (Anolis carolinensis). Ethology 107:777–793.
Yodyingyuad, U., C. de la Riva, D. H. Abbott, J. Herbert, and E. B.
Keverne. 1985. Relationship between dominance hierarchy, cerebrospinal fluid levels of amine transmitter metabolites (5-hydroxyindole acetic acid and homovanillic acid) and plasma cortisol in monkeys. Neuroscience 16:851–858.