Serotonin-1A receptor activity and expression modulate adolescent anabolic/androgenic steroid-induced aggression in hamsters

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 2006-09, Vol.85 (1), p.1-11
• Main Authors: Ricci, Lesley A., Rasakham, Khampaseuth, Grimes, Jill M., Melloni, Richard H.
• Format: Article
• Language: English
• Subjects: 8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology; Adolescence; Aggression; Aggression - drug effects; Anabolic Agents - pharmacology; Anabolic–androgenic steroids; Androgens - pharmacology; Animals; Anterior hypothalamus; Biological and medical sciences; Cricetinae; Development; Dose-Response Relationship, Drug; Immunohistochemistry; Male; Medical sciences; Mesocricetus; Receptor, Serotonin, 5-HT1A - metabolism; Receptor, Serotonin, 5-HT1A - physiology; Serotonin; Serotonin 1A receptor; Serotonin 5-HT1 Receptor Agonists
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2006.06.022

Repeated high dose (5.0 mg/kg) anabolic/androgenic steroid exposure during adolescence stimulates offensive aggression in male Syrian hamsters. These studies examined whether anabolic/androgenic steroid-induced aggression was regulated by the activity and expression of serotonin (5HT) type-1A receptors. In a first experiment, adolescent male hamsters were treated with a mixture of anabolic/androgenic steroids and then scored for offensive aggression in the absence or presence of the selective 5HT1A receptor agonist R(+)-8-OH-DPAT (0.1–0.6 mg/kg). Adolescent anabolic/androgenic steroid-treated hamsters displayed high levels of offensive aggression that could be reversed by enhancing the activity of 5HT1A receptors. The agonist R(+)-8-OH-DPAT dose-dependently reduced the steroid-induced aggressive response, with significant reductions in aggression observed at 0.1–0.3 mg/kg. In a second set of experiments, adolescent hamsters were administered anabolic/androgenic steroids or vehicle and then examined for 5HT1A receptor localization and expression in regions of the brain important for aggression control. Hamsters treated with anabolic/androgenic steroids showed significant decreases in 5HT1A receptor-immunoreactive staining and protein levels in the anterior hypothalamus (i.e., a brain region central to the control of offensive aggression in hamsters) with no concomitant decrease in the number of 5HT1A receptor-expressing neurons. Together, these data support a role for site-specific down-regulation of 5HT1A receptor activity in adolescent anabolic/androgenic steroid-induced aggression.