Parasite manipulation of brain monoamines in California killifish (Fundulus parvipinnis) by the trematode Euhaplorchis californiensis.

California killifish (Fundulus parvipinnis) infected with the brain-encysting trematode Euhaplorchis californiensis display conspicuous swimming behaviours rendering them more susceptible to predation by avian final hosts. Heavily infected killifish grow and reproduce normally, despite having thousands of cysts inside their braincases. This suggests that E. californiensis affects only specific locomotory behaviours. We hypothesised that changes in the serotonin and dopamine metabolism, essential for controlling locomotion and arousal may underlie this behaviour modification. We employed micropunch dissection and HPLC to analyse monoamine and monoamine metabolite concentrations in the brain regions of uninfected and experimentally infected fish. The parasites exerted density-dependent changes in monoaminergic activity distinct from those exhibited by fish subjected to stress. Specifically, E. californiensis inhibited a normally occurring, stress-induced elevation of serotonergic metabolism in the raphae nuclei. This effect was particularly evident in the experimentally infected fish, whose low-density infections were concentrated on the brainstem. Furthermore, high E. californiensis density was associated with increased dopaminergic activity in the hypothalamus and decreased serotonergic activity in the hippocampus. In conclusion, the altered monoaminergic metabolism may explain behavioural differences leading to increased predation of the infected killifish by their final host predators.

Early life social isolation alters corticotropin-releasing factor responses in adult rats.

Stress induced by early life social isolation leads to long-lasting alterations in stress responses and serotonergic activity. Corticotropin-releasing factor (CRF) is a neurotransmitter that mediates stress responses and alters serotonergic activity. We tested the hypothesis that the stress of early life isolation enhances responses to CRF in adulthood by determining the effect of CRF infusions into the dorsal raphe nucleus (dRN) on 5-HT release in the nucleus accumbens (NAc) of adult rats using in vivo microdialysis. Juvenile male rats were either isolated or housed in groups of three for a 3-week period beginning on postnatal day 21 after which, all rats were group-reared for an additional 2 weeks. Following the isolation/re-socialization procedure, infusion of 100 ng CRF into the dRN decreased 5-HT release in the NAc of group-reared rats. This treatment did not significantly affect 5-HT release in the NAc of isolation-reared animals. In contrast, infusion of 500 ng CRF into the dRN transiently increased 5-HT release in the NAc of both group-reared and isolated animals with isolated animals showing a more prolonged serotonergic response. Western blot and immunofluorescent staining for CRF receptors in the dRN showed that CRF(2) receptor levels were increased in the dRN of isolation-reared animals when compared with group-reared rats. Taken together, the results suggest that isolation during the early part of development causes alterations in both CRF receptor levels and CRF-mediated serotonergic activity. These effects may underlie the increased sensitivity to stress observed in isolates.

Corticotropin releasing factor influences aggression and monoamines: modulation of attacks and retreats.

Salmonids establish social hierarchies as a result of aggressive social interactions. The establishment of dominant or subordinate status is strongly linked to neuroendocrine responses mediated through the stress axis. In this study, we tested the effects of introcerebroventricular (icv) corticotropin releasing factor (CRF) on the behavioral outcome, plasma cortisol and monoamine function in trout subjected to a socially aggressive encounter. Rainbow trout were treated with an icv injection of artificial cerebrospinal fluid (aCSF), 500 or 2000 ng ovine CRF, or not injected. Fish were allowed to interact with a similarly sized conspecific for 15 min. Following the behavioral interaction, plasma cortisol and central monoamine concentrations were analyzed. Trout treated with CRF were victorious in approximately 66% of the aggressive encounters against aCSF-treated opponents. Trout injected with CRF exhibited a reduction in the total number of attacks and decreased latency to attack. When trout were divided into winners and losers, only victorious CRF-treated fish exhibited a reduced latency to attack and fewer retreats. Social stress increased cortisol levels in both winners and losers of aggressive interaction. This effect was enhanced with the additional stress incurred from icv injection of aCSF. However, icv CRF in addition to social stress decreased plasma cortisol in both winners and losers. While aggression stimulated significant changes in serotonergic and dopaminergic activity, the magnitude and direction were dependent on limbic brain region, CRF dose, and outcome of social aggression. With broad effects on aggressive behavior, anxiety, stress responsiveness, and central monoaminergic activity, CRF plays an important role in modulating the behavioral components of social interaction.

Corticotropin-releasing factor in the dorsal raphe elicits temporally distinct serotonergic responses in the limbic system in relation to fear behavior.

The neurotransmitters serotonin and corticotrophin-releasing factor are thought to play an important role in fear and anxiety behaviors. This study aimed to determine the relationship between corticotrophin-releasing factor-evoked changes in serotonin levels within discrete regions of the limbic system and the expression of fear behavior in rats. The effects of corticotrophin-releasing factor administration to the serotonin cell body regions of the dorsal raphe nucleus on fear behavior, behavioral activity, and extracellular serotonin levels were assessed in freely moving rats with microdialysis probes implanted into the central nucleus of the amygdala and the medial prefrontal cortex. Infusion of corticotrophin-releasing factor (0.5 microg) into the dorsal raphe rapidly induced freezing behavior, which was positively correlated with an immediate increase in serotonin release in the central nucleus of the amygdala. In contrast, cessation of freezing behavior correlated with a delayed and prolonged increase in serotonin release within the medial prefrontal cortex. Our findings suggest that corticotrophin-releasing factor-induced freezing behavior is associated with regionally and temporally distinct serotonergic responses in the limbic system that may reflect differing roles for these regions in the expression of fear/anxiety behavior.

Social stress and corticosterone regionally upregulate limbic N-methyl-D-aspartatereceptor (NR) subunit type NR(2A) and NR(2B) in the lizard Anolis carolinensis.

Social aggression in the lizard Anolis carolinensis produces dominant and subordinate relationships while elevating corticosterone levels and monoaminergic transmitter activity in hippocampus (medial and mediodorsal cortex). Adaptive social behavior for dominant and subordinate male A. carolinensis is learned during aggressive interaction and therefore was hypothesized to involve hippocampus and regulation of N-methyl-d-aspartate (NMDA) receptors. To test the effects of social stress and corticosterone on NMDA receptor subunits (NR), male lizards were either paired or given two injections of corticosterone 1 day apart. Paired males were allowed to form dominant-subordinate relationships and were killed 1 day later. Groups included isolated controls, dominant males, subordinate males and males injected with corticosterone. Brains were processed for glutamate receptor subunit immunohistochemistry and fluorescence was analyzed by image analysis for NR(2A) and NR(2B) in the small and large cell divisions of the medial and mediodorsal cortex. In the small granule cell division there were no significant differences in NR(2A) or NR(2B) immunoreactivity among all groups. In contrast, there was a significant upregulation of NR(2A) and NR(2B) subunits in the large pyramidal cell division in all three experimental groups as compared with controls. The results revealed significantly increased NR(2A) and NR(2B) subunits in behaving animals, whereas animals simply injected with corticosterone showed less of an effect, although they were significantly increased over control. Upregulation of NR(2) subunits occurs during stressful social interactions and is likely to be regulated in part by glucocorticoids. The data also suggest that learning social roles during stressful aggressive interactions may involve NMDA receptor-mediated mechanisms.

Serotonergic response to social stress and artificial social sign stimuli during paired interactions between male Anolis carolinensis.

Serotonergic activity is influenced by social status and manipulation of social signals. In the lizard Anolis carolinensis, eyespot formation, i.e. darkening of postorbital skin from green to black, appears during stressful and agonistic situations, forming first in males that become dominant. To assess the effect of eyespots on central serotonergic activity during social interaction, males were paired by weight and painted postorbitally with green or black paint. Manipulation of eyespot color influenced social interactions and status. All males that viewed an opponent with black painted eyespots became subordinate. In these subordinate animals, serotonergic activity was elevated in hippocampus, striatum, nucleus accumbens and locus ceruleus. In contrast, males that viewed opponents with hidden eyespots (painted green) and became dominant had increased serotonergic activity in hypothalamus, medial amygdala and raphé. Pre-painted eyespots produced results that distinguish dominant and subordinate relationships based on serotonergic activity not previously seen in unmanipulated pairs. Results from experiments using pairs are similar to those using mirrors for medial amygdala and locus ceruleus, but not hippocampus, nucleus accumbens or raphé. Decreased hypothalamic serotonin was associated with increased aggressive behavior. These results, when compared with previous studies, suggest some flexibility in central serotonergic systems, which may shape dominant and subordinate rank acquisition, and appear to be influenced by the completion of social role formation. Furthermore, social status and central serotonergic activity was influenced by a visual cue, the presence or absence of postorbital eyespots on an opponent.

Monoaminergic activity in subregions of raphé nuclei elicited by prior stress and the neuropeptide corticotropin-releasing factor.

Corticotropin-releasing factor (CRF) coordinates neuroendocrine responses to stressful stimuli; one mechanism through which CRF may modulate hypothalamic-pituitary-adrenal axis activity is via actions on neuromodulatory systems such as serotonergic systems. Recent electrophysiological studies and the distribution of CRF receptors within midbrain and pontine raphé nuclei suggest that stress and CRF may have actions on topographically organized subpopulations of serotonergic neurones. We compared the effects of vehicle or intracerebroventricular r/hCRF injections (0, 0.1, 1 or 10 micro g) in rats previously maintained in home cages or restrained for 1 h, 24 h before injection, on monoamine and monoamine metabolite tissue concentrations in the dorsal (lateral wings, rostral midline, caudal midline), median (rostral, caudal) and interfascicular raphé subdivisions of the midbrain and pontine raphé nuclei, using brain microdissection and high-performance liquid chromatography with electrochemical detection. At the lowest dose studied (0.1 micro g), CRF infusions in previously stressed rats decreased 5-hydroxytryptophan (5-HTP) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations only within the rostral median raphé nucleus. At higher doses, CRF infusions in previously stressed rats increased tissue concentrations of 5-HTP, serotonin (5-HT), or the serotonin metabolite, 5-HIAA, within rostral (but not caudal) regions of the median and dorsal raphé nuclei. By contrast, restraint stress alone had no effect on tissue concentrations of 5-HTP, 5-HT or 5-HIAA measured 24 h later in any subdivision, while CRF injections in rats not previously exposed to restraint stress, with few exceptions, also had no effect. These results suggest that the effects of CRF on serotonergic function are context-dependent, dose-dependent, and regionally specific within subdivisions of the brainstem raphé nuclei.

Monoaminergic changes associated with socially induced sex reversal in the saddleback wrasse.

The process of sex reversal in fishes is socially mediated and requires a total reorganization of the hypothalamo-pituitary-gonadal axis. When the ratio of males to females in a population of saddleback wrasse (Thalassoma dupperrey) is too low, the largest female becomes male over the course of 6 to 8 weeks. This event requires the conversion of external social cues into internal chemical cues. In an attempt to investigate the role monoamines might play in this process, two females were housed together in floating enclosures in order to induce sex reversal in the larger. Brains were sampled at various time points throughout the process of sex reversal. Monoamines were measured in the amygdala, preoptic area, ventral hypothalamus, locus coeruleus and raphe nucleus. Changes were demonstrated in monoamine metabolism for all brain regions examined. The most important changes in monoamine-system activation were seen during the first week of sex reversal. It is during this time that transitional animals undergo behavioral sex reversal. There is an increase in serotonergic activity in the amygdala which is likely related to territorial acquisition. The absence of male aggression results in a less stressful environment for the female and a reduction in serotonergic activity in the preoptic area allowing for an increase in noradrenergic activity potentially triggering the reorganization of the reproductive axis. In the ventral hypothalamus, there is a decrease in noradrenergic and increase in dopaminergic activity associated with this change from female to male. The locus coeruleus shows an increase in noradrenergic activity later in the process of sex reversal which is probably a response to more circulating androgens. In the raphe nucleus, there is a decrease in serotonergic activity at the time of behavioral sex reversal. This decrease in serotonergic activity is linked to the behavioral component of sex reversal. This study suggests that monoamines play a very important role in both behavioral and gonadal sex reversal in the saddleback wrasse, the former under the control of serotonin in the raphe and the latter mediated via serotonergic effects on norepinephrine in the preoptic area.

Temporal patterns of limbic monoamine and plasma corticosterone response during social stress.

Dominant and subordinate males respond differently to the stress of social interaction. After an hour of social interaction, subordinate male Anolis carolinensis have elevated serotonergic activity in hippocampus, but dominant males do not. In other species, and using other stressors, the activation of hippocampal serotonergic activity is much more rapid than one hour. To elucidate early stress responsiveness, adult male A. carolinensis were divided into four groups: isolated controls, and pairs of males sampled after 10, 20 or 40 minutes of aggressive interaction. Development of dominant-subordinate relationships was determined by behavior and by the celerity of eyespot darkening. Serotonergic activity in the hippocampus, nucleus accumbens and amygdala was elevated rapidly and equally in both dominant and subordinate males, as were plasma corticosterone concentrations. Serotonergic activity remained elevated through 40 minutes in hippocampus and nucleus accumbens. Only subordinate males had elevated corticosterone levels at 40 minutes. Social status does not impede socially induced stress responses. Rather, rapid regulation of serotonergic stress responses appears to be a mediating factor in determining both behavioral output and social status. Temporal expressions of monoaminergic and endocrine stress responses are distinctive between males of dominant and subordinate social status. Such temporal patterns of transmitter and glucocorticoid activity may reflect neurocircuitry adaptations that result in behavior modified to fit social status.

The role of monoaminergic nuclei during aggression and sympathetic social signaling.

A social sign stimulus that is sympathetically induced affects aggressive approaches and influences serotonergic, dopaminergic and noradrenergic activity in the brainstem nuclei of Anolis carolinensis. Darkening of postorbital skin via sympathetic activation of adrenal catecholamines and beta(2)-adrenergic receptors provides a visual signal that forms more rapidly in dominant than subordinate males during social interactions. This signal limits aggressive interactions. Males were painted postorbitally with green or black paint and then exposed to a mirror. Aggressive approaches to the mirror were inhibited in males viewing a reflection with darkened eyespots, and increased in males viewing a reflection without eyespots (hidden). Noradrenergic turnover in the raphe and locus ceruleus were greatest in test subjects that viewed a reflection with eyespots hidden by green paint. Perception of darkened eyespots stimulated greater serotonergic turnover in raphe, locus ceruleus and substantia nigra/ventral tegmental area (SN/VTA). Dopaminergic turnover was higher in the raphe and SN/VTA of Anolis that viewed a reflection with darkened eyespots. However, these animals had lower dopamine turnover in the locus ceruleus than isolated and hidden eyespot groups. Of the possible roles of perikarya on central function and behavior, our results suggest feedback, cross-nuclear regulation, and some independence of function between nuclei and the forebrain terminal fields. Decreased serotonergic activity corresponds with increased aggression only in the raphe, suggesting that the raphe nuclei might be important for this behavioral trait. Increased serotonergic, noradrenergic and dopaminergic activities in SN/VTA in Anolis that view a reflected opponent with dark eyespots suggests that the SN/VTA might be directly involved in recognition of this social sign stimulus and the resulting inhibition of aggression.

Mechanisms for quick and variable responses.

Dominant and subordinate males produce neuroendocrine stress responses during aggressive social interaction. In addition, stress responsiveness has both acute and chronic temporal components. A neurochemical marker that distinguishes social status and aggression by temporal and regional differentiation is the activity of serotonergic nuclei and terminals. A unique model for distinguishing the relationships among the neuroendocrine machinery of stress, social status and behavior is the lizard Anolis carolinensis. Dominant males exhibit more aggression and have temporally advanced serotonergic responses. Chronic serotonergic activity is associated with subordinate social status and reduced aggression. Acute and chronic serotonergic responses occur in both dominant and subordinate males, and are distinguished temporally. This provides a fundamental question that may elucidate basic differences in behavior: What causes temporally advanced serotonergic activity in response to stress in dominant males? Secondarily, what is the neural basis for the acute and chronic responses? The neural mechanisms for transduction of the relevant behavioral signals are very plastic. Behavioral experience and visual stimuli can produce very rapid responses. Faster and greater responsiveness may be stimulated by restraint stress, social stress and the absence of social sign stimuli (e.g. eyespots of the lizard Anolis carolinensis). Stress response machinery provides regulatory factors necessary to modify social behavior, and to adapt it for specific contexts. Serotonergic activity is rapidly modified by glucocorticoids and GABA, and also by CRF under conditions of previous stress or in combination with AVP. Advancing acute elevation of serotonergic activity may be a distinguishing characteristic of dominant males. Social events add contextual conditioning to brain transmitter activity, with social information processed in a distributed fashion. Medial amygdala manifests delayed serotonergic response compared to hippocampus and nucleus accumbens, and is therefore a good candidate to mediate chronic stress responsiveness. Limiting or delaying acute effects, in addition to chronic serotonergic activity, may be the distinguishing characteristics of subordinate males. Monoamines, glucocorticoids, testosterone, CRF, AVP, AVT, play neuromodulatory roles producing context appropriate behavior.

Serotonin reverses dominant social status.

Social stress from aggressive interaction is expressed differently in specific brain regions of dominant and subordinate male Anolis carolinensis. Prior to aggressive behavior, the outcome is predictable via the celerity of postorbital coloration: Dominant males exhibit more rapid eyespot darkening. Serotonergic activation is manifest rapidly (1 h) in hippocampus, nucleus accumbens and brainstem of subordinate males, and is expressed more rapidly in dominant males. Amygdalar serotonergic activation responds rapidly (1 h) in dominant males, but is expressed slowly (1 w) and chronically in subordinate males. We hypothesized that chronic (1 w) serotonin elevation, manipulated by the selective serotonin reuptake inhibitor sertraline, would decrease aggressiveness and result in subordinate status. Dominant status was established in pairs of male A. carolinensis. The pairs were separated and treated with sertraline or vehicle. Sertraline was given in food to either the dominant or the subordinate male, both males or neither male for 1 week. Pairs were reintroduced, and behavior and social status recorded. When both dominant and subordinate males were treated with sertraline (or vehicle), or when subordinate males alone were treated with sertraline, previously established social relationships remained unchanged or became associative. However, when dominant males alone were treated with sertraline, their social status was reversed (43%) or negated (57%). Latency to eyespot darkening was significantly retarded in dominant males treated with sertraline, and aggressive displays and attacks were reduced. Chronic 5-HT elevation is consistent with subordinate status. Social status and aggressive disposition do not appear to be immutable, but may be changed by neuroendocrine mechanisms that mediate adaptation to environmental conditions like stress.

Visible sympathetic activity as a social signal in Anolis carolinensis: changes in aggression and plasma catecholamines.

Darkening of postorbital skin in Anolis carolinensis occurs during stressful situations and is stimulated by sympathetic activation of beta(2)-adrenergic receptors via adrenal catecholamines. This eyespot forms more rapidly in dominant males during social interaction. Eyespot darkening (green to black) appears to function as a social signal communicating sympathetic activation and limiting aggressive interaction. To assess the value of the eyespot as a social signal, males were painted postorbitally with green, black, or red paint. Each male was exposed to a mirror following acclimation to the cage. The total number of aggressive displays toward the mirror image was greatest when eyespots were masked by green paint. In contrast, black or red artificial eyespots, regardless of size, inhibited biting behavior toward the mirror image. The most aggressive males, those who saw a reflected opponent with no eyespot (hidden with green paint), had significantly higher levels of all plasma catecholamines. These results suggest that A. carolinensis use information from the eyespot to assess their opponent's readiness to fight and thereby determine whether to be aggressive. Darkened eyespots are capable of inhibiting aggression, whereas aggressive displays from an opponent in the mirror without darkened eyespots do not. Darkened eyespots reflect rapid changes in plasma NE, DA, and Epi that may signal dominant social status.

Stress induces rapid changes in serotonergic activity: restraint and exertion.

Rapid activation of central serotonergic systems occurs in response to the social stress of aggression in dominant lizards. The most rapid expression of serotonergic activity occurs in nucleus accumbens, hippocampus and brainstem. To compare previously measured responses induced by social stressors with those provoked by physical stress, serotonergic activity was examined following restraint stress (handling) and forced physical exertion. After handling, some male Anolis carolinensis were placed on a race track and either run until there was no movement following 1 min of prodding, or half that time. Controls were killed without treatment. Lizards stressed by handling showed rapid (25 s) increases in serotonergic activity (5-HIAA/5-HT) in striatum, dorsal cortex, locus ceruleus, and nucleus accumbens. Other changes in serotonergic systems caused by stress occurred in raphe and hippocampus. Serotonergic changes induced by handling stress were reversed by exercise (to 50% maximal exertion time) in subiculum, striatum and nucleus accumbens. The serotonergic profile of lizards run until they would no longer respond to prodding (maximal exertion time) was significantly different from that for more acute exertion in hippocampus, subiculum, striatum, medial amygdala, locus ceruleus, area postrema, and raphe. Physical stress (handling) mimicked social stress by producing rapid serotonergic changes in hippocampus, subiculum, nucleus accumbens and locus ceruleus. In contrast, the medial amygdala, which has previously been demonstrated to respond serotonergically to social stress only after a temporal delay, did not show a rapid response to restraint stress.

Monoaminergic activities of limbic regions are elevated during aggression: influence of sympathetic social signaling.

A visual social signal inhibiting aggression is coincident with limiting serotonergic and noradrenergic activity in subiculum, hippocampus, nucleus accumbens, medial amygdala, but not lateral amygdala, septum, and hypothalamus. Darkening of postorbital skin in the lizard Anolis carolinensis is stimulated by sympathetic activation of beta(2)-adrenergic receptors via adrenal catecholamines, and occurs more rapidly in dominant males during social interaction. Eyespot darkening functions as a social signal limiting aggressive interaction. To assess the effect of this social signal on telencephalic activity of monoamines, males were painted postorbitally with green or black paint, and exposed to a mirror. Serotonergic and noradrenergic turnover, as estimated by ratios of catabolite to transmitter, were elevated in the subiculum, hippocampus, nucleus accumbens, and medial amygdala of animals in which the eyespots were masked by green paint. Conversely, dopaminergic activity in these brain regions was lower in males with hidden eyespots (painted green). Hiding the eyespot evoked significantly increased aggressive activity toward the mirror image. Furthermore, changes in monoaminergic turnover were coincident with altered aggressive behavior, suggesting a relationship between them. Changes of monoaminergic activity were not observed in the septum, lateral amygdala, or hypothalamus, when males with eyespots permanently marked (black) were compared with those with eyespots hidden (painted green). Stimulated (serotonergic and noradrenergic) or inhibited (dopaminergic) activity due to social signal and aggression are confined to regions of the brain similarly activated during social stress, and do not constitute a generalized activation of monoaminergic systems.

Serotonergic responses to corticosterone and testosterone in the limbic system.

Glucocorticoids secreted peripherally during stressful events act on central monoaminergic systems. In particular, serotonergic mediation of social behavior, such as aggression and reproduction, may be affected by glucocorticoids. This study was undertaken to determine if systemically administered corticosterone would rapidly affect central monoaminergic activity. Male Anolis carolinensis (N = 8 each group) were injected intraperitoneally with 10 or 100 micrograms corticosterone, 10 micrograms testosterone, or saline. Twenty minutes after treatment, brains were rapidly dissected and frozen and then microdissected (punch diameter 300 microm) and analyzed by high-performance liquid chromatography. Serotonergic turnover (estimated by 5-hydroxyindoleacetic acid/serotonin) in the hippocampus and medial amygdala was significantly enhanced by systemic corticosterone. Both of these regions of the brain have been associated with social stress. Testosterone also enhanced turnover in the hippocampus. The effect of corticosterone and testosterone may be to modulate socially induced differences in serotonergic response. Rapid, but short-lived, glucocorticoid stimulation of serotonin release suggests a possible mechanism for mediation of changing social behavioral events.

Lateralized effects of ethanol on aggression and serotonergic systems in Anolis carolinensis.

The lateralized effects of ethanol (ETOH) upon behavior and monoamine biochemistry in the lizard, Anolis carolinensis, were examined. Eight adult male anoles consumed solutions of 19% ethanol (ETOH) twice daily over the course of 18 days, while controls consumed water. ETOH decreased the use of the left eye/right hemisphere, but not the right eye/left hemisphere, during territorial aggression (p<0.05). During crossover (i.e., ETOH to water and vice versa) this effect was reversible and replicable. Biochemically, an asymmetry was observed in 5-HT levels in the raphe both in ETOH and controls. ETOH increased levels of serotonin (5-HT; p<0.05), and 5-HIAA/5-HT ratios (p<0.05) in the raphe; serotonin levels in several brain regions correlated with aggressive responses. These results suggest that ETOH boosts 5-HT levels in animals subchronically exposed to ETOH. They further suggest that asymmetry in endogenous 5-HT systems may account for the asymmetrical regulation of aggression generally, and may explain the behavioral effects of ETOH upon lateralized aggression.

Regional and temporal separation of serotonergic activity mediating social stress.

Stressful aggressive interaction stimulates central serotonergic activation in telencephalon as well as brainstem. Social roles can be distinguished by monoamine activity following aggression. Pairs of male lizards, Anolis carolinensis, were allowed to fight and form dominant/subordinate relationships. In micropunched regions of telencephalon, the greatest serotonergic changes occur in subordinate males. In hippocampal cortex and nucleus accumbens, subordinate males have increased 5-hydroxyindoleacetic acid/serotonin at 1 h following the fight. In these areas the ratio gradually decreases over a week of cohabitation, as was previously reported for brainstem. Medial and lateral amygdala develop increased serotonergic activity more slowly, with the greatest increase being evident following a week of interaction. Turnover, serotonin and 5-hydroxyindoleacetic acid levels in amygdala escalate over the first week of interaction in subordinate males, and return to baseline by one month. In dominant males, the pattern is accelerated, with the most extensive serotonin system activity present at 1 h, then decreasing over a month. The patterns of serotonergic activation are so similar in hippocampus, nucleus accumbens and brainstem that a co-ordinated response may be involved in mediating short-term social stress and aggression. Similarly, medial and lateral amygdala exhibit corresponding, but delayed patterns in subordinate males, suggesting a co-ordinated response in these regions mediating longer-term stress responses. These data are consistent with rapid neuroendocrine stress modulation in dominant individuals, and delayed serotonergic activity changes in subordinate males.