Serotonin 5-HT1A receptor in infancy-onset aggression: Comparison with genetically defined aggression in adult rats

Antisocial aggressive behavior in adolescents represents growing clinical and social problem. Previously the implication of 5-HT1A receptor in the regulation of fear-induced aggression was shown. Here, the involvement of 5-HT1A receptor in infancy-onset genetically defined aggression was studied on Norway rats selectively bred for high level or for the lack of aggression toward man. The aggressive behavior and the expression of 5-HT1A receptor gene, 5-HT1A receptor density and functional activity were determined in infant (15-day-old) and adult rats. Considerable differences in aggressive response to man between infant rats of aggressive (A) and nonaggressive (NA) strains were found. In contrast to infant NA rats, A infants elicited marked aggressive response to handling, although its expression was less than in adult A rats. 5-HT1A receptor agonist 8-OH-DPAT (0.2 and 0.5 mg/kg) decreased aggressive behavior in both A infant and adult rats. The desensitization of 5-HT1A receptors in the brain of A infant and adult rats was revealed. In contrast to decreased 5-HT1A gene expression in the midbrain of A adult rats, the 5-HT1A gene expression in the midbrain of infant rats did not differ between A and NA strains. There was no difference in 5-HT1A receptor density in infant rats. The data showed (1) the implication of 5-HT1A receptor in genetically defined infancy-onset fear-induced aggression, (2) the desensitization of 5-HT1A receptors as essential factor in infancy-onset aggression, and (3) the increased complexity of 5-HT-ergic control of aggressive behavior in adult rats with the involvement of 5-HT1A gene and the density of 5-HT1A receptors.

► 15-day-old rats of aggressive strain demonstrate increased level of aggression.
► Selective breeding for fear-induced aggression desensitizes 5-HT1A receptors.
► 5-HT1A receptor functional activity already reduced in aggressive rat pups.
► 5-HT1A gene expression was decreased in aggressive adult but not infant rats.
► 5-HT1A receptor inhibits fear-induced aggression in both adult and infant rats.