Serotonin and arginine-vasopressin mediate sex differences in the regulation of dominance and aggression by the social brain.
There are profound sex differences in the incidence of many psychiatric disorders. Although these disorders are frequently linked to social stress and to deficits in social engagement, little is known about sex differences in the neural mechanisms that underlie these phenomena. Phenotypes characterized by dominance, competitive aggression, and active coping strategies appear to be more resilient to psychiatric disorders such as posttraumatic stress disorder (PTSD) compared with those characterized by subordinate status and the lack of aggressiveness. Here, we report that serotonin (5-HT) and arginine-vasopressin (AVP) act in opposite ways in the hypothalamus to regulate dominance and aggression in females and males. Hypothalamic injection of a 5-HT1a agonist stimulated aggression in female hamsters and inhibited aggression in males, whereas injection of AVP inhibited aggression in females and stimulated aggression in males. Striking sex differences were also identified in the neural mechanisms regulating dominance. Acquisition of dominance was associated with activation of 5-HT neurons within the dorsal raphe in females and activation of hypothalamic AVP neurons in males. These data strongly indicate that there are fundamental sex differences in the neural regulation of dominance and aggression. Further, because systemically administered fluoxetine increased aggression in females and substantially reduced aggression in males, there may be substantial gender differences in the clinical efficacy of commonly prescribed 5-HT-active drugs such as selective 5-HT reuptake inhibitors. These data suggest that the treatment of psychiatric disorders such as PTSD may be more effective with the use of 5-HT-targeted drugs in females and AVP-targeted drugs in males.
Neuroscience Institute, Georgia State University, Atlanta, GA 30303.|Center for Behavioral Neuroscience, Georgia State University, Atlanta, GA 30303.
Joseph I
JI
Terranova
Neuroscience Institute, Georgia State University, Atlanta, GA 30303.|Center for Behavioral Neuroscience, Georgia State University, Atlanta, GA 30303.
Zhimin
Z
Song
Neuroscience Institute, Georgia State University, Atlanta, GA 30303.|Center for Behavioral Neuroscience, Georgia State University, Atlanta, GA 30303.
Tony E
TE
Larkin
Neuroscience Institute, Georgia State University, Atlanta, GA 30303.|Center for Behavioral Neuroscience, Georgia State University, Atlanta, GA 30303.
Nathan
N
Hardcastle
Neuroscience Institute, Georgia State University, Atlanta, GA 30303.|Center for Behavioral Neuroscience, Georgia State University, Atlanta, GA 30303.
Alisa
A
Norvelle
Neuroscience Institute, Georgia State University, Atlanta, GA 30303.|Center for Behavioral Neuroscience, Georgia State University, Atlanta, GA 30303.
Ansa
A
Riaz
Neuroscience Institute, Georgia State University, Atlanta, GA 30303; biohea@gsu.edu.|Center for Behavioral Neuroscience, Georgia State University, Atlanta, GA 30303.
H Elliott
HE
Albers
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000374:Aggression / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001127:Arginine Vasopressin / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008647:Mesocricetus; D012701:Serotonin / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D012727:Sex Characteristics; D012930:Social Dominance
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D001127:Arginine Vasopressin; D005473:Fluoxetine; D012701:Serotonin; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors
agonistic; fluoxetine; gender differences; hamster; social behavior