Research report
Serotonin reverses dominant social status

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Abstract

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.

Introduction

Expression of social behavior often results in alteration of monoaminergic activity [48]. Serotonin (5-HT) is associated with locomotion [3], feeding [46], asymmetry of alcohol effects [11], depression [2], [27], stress [14], [29], and aggression [20], [34]. Aggression is inversely correlated with serotonergic activity [11], [15], [42], [43], and numerous studies employing selective 5-HT reuptake inhibitors have demonstrated a reduction in aggressive behavior following increased serotonergic activity resulting from treatment [15], [22], [31], [32], [35], [45]. The anti-aggressive effects of serotonin have been demonstrated in the lizard Anolis carolinensis by Deckel and colleagues [9], [10] using the 5-HT reuptake inhibitor fluoxetine (Prozac). Serotonergic activity has also been correlated with social status in primates [34], [54], other mammals [4], [5], [29], reptiles [28] and fishes [49], [50], [51].

The correlation between monoaminergic activity and social status suggests the possibility that monoamines play a causal role determining dominant–subordinate relationships. A variety of experiments sampled from across the animal kingdom imply this possibility. Queen bees have significantly more dopamine and norepinephrine than worker bees [7]. Aggression and social dominance have been stimulated in fish by treatment with l-dopa [47]. In crustaceans, serotonin mediates development of the neural substrates necessary for establishment of dominant status [52], [53]. Injections of 5-HT into the hemolymph can push subordinate crayfish or lobsters into aggressive behavior, which temporarily contributes to a dominant role [20]. Serotonergic drugs or lesion of the raphe of rats can alter dominant control of access to drinking water [25]. Therefore, monoamines, especially serotonin, appear to be important for both aggressive behavior and social status in a range of species.

In the lizard Anolis carolinensis, there are temporal differences in regional serotonergic activity between dominant and subordinate males. While serotonergic responses appear to be expressed in the same regions of the brain in both dominant and subordinate lizards, the timing of the response is substantially different [41]. Celerity-dependent neuroendocrine events appear to coordinate establishment of social status [41]. In the medial amygdala, a structure associated with stimulation of adrenal axis stress hormones [13], [19], serotonergic activity is elevated within an hour of initiation of fighting in dominant males [41]. Subordinate males however, do not exhibit enhanced serotonergic activity in medial amygdala until 24 h after agonistic behavior begins. Peak levels of serotonergic activation in subordinate males are not reached until 1 week of cohabitation. Differences in central neurochemical state between dominant and subordinate males are reflected externally in the skin color of this lizard.

A unique visible indicator of social status is manifest by Anolis carolinensis: The rate of darkening of postorbital skin (eyespot). During establishment of dominant–subordinate relationships, the skin just behind the eye darkens (as with any stress), and it does so most quickly in males that become dominant [38]. Rapid darkening of the eyespot is a social sign stimulus that significantly inhibits aggression [23], [24]. Eyespot darkening is a function of sympathetic activity, via endocrine activation of β2 adrenergic receptors [18]. Therefore, more rapid serotonergic and autonomic activation appears to be a central neurochemical trait that characterizes dominant male status.

Because neuroendocrine responsiveness appears to be faster and more brief in dominant males, it was hypothesized that the duration of serotonergic activity played an important role in determining social status. The purpose of this study was to mimic chronically elevated serotonergic activity of subordinate males using a selective serotonin reuptake inhibitor to affect social behavior. Specifically, it was hypothesized that sertraline (=Zoloft; Pfizer) would reduce aggression, delay eyespot darkening and promote submissive behavior.

Section snippets

Animals

Adult, sexually active male (>57 mm snout–vent length) Anolis carolinensis were obtained from a commercial supplier (Buck's Live Animals, La Place, LA). Each was weighed, measured and then matched with a counterpart that differed by no more than 0.5 g and 2 mm. Animals were marked on the tail with either white or yellow paint [1] and placed in glass terraria (51×30×26cm) on opposite sides of an opaque divider. All lizards were allowed to acclimate for 1 week during which time they were watered

Results

Dominant–subordinate relationships followed aggressive interaction in 30 of 32 pairs initially interacting. Of 30 pairs with clearly defined social status, 24 were subsequently used for drug treatment. In a few cases, aggressive interaction was so intense that subordinate males died (although not from obvious wounds). As in previous experiments, eyespot was a reliable predictor of social dominance [38]. Males with more rapid darkening of the postorbital eyespot became dominant in 95% of the

Discussion

Sertraline effectively reduced aggressive behavior in the lizard A. carolinensis. Pairs of lizards not treated with sertraline showed no decrease in aggressive behavior of the dominant male during the second set of interactions. Subordinate males in the untreated group exhibited no aggression at all, perhaps reflecting prior establishment of social hierarchy. Decreased aggressiveness by treated dominant males was evident in the associative relationships that were adopted after administration of

Acknowledgements

We thank Pfizer for the gift of sertraline, Karen Olmstead for aid with statistical analyses, and Tangi R. Summers for helpful comments on this manuscript. Supported by NSF grant OSR-9452894 and NIH grant P20 RR15567.

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    Present address: Department of Neuroscience, Uppsala University, Uppsala, SE-75124, Sweden.

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