Research ReportsValproate selectively suppresses adolescent anabolic/androgenic steroid-induced aggressive behavior: implications for a role of hypothalamic γ-aminobutyric acid neural signalingLee, Terrence J.*,; Zanello, Andrea F.*,; Morrison, Thomas R.; Ricci, Lesley A.; Melloni, Richard H. Jr. Author Information Program in Behavioral Neuroscience, Department of Psychology, Northeastern University, Boston, Massachusetts, USA *Terrence J. Lee and Andrea F. Zanello contributed equally to the writing of this article. Received 10 February 2020 Accepted as revised 19 November 2020 Correspondence to Richard H. Melloni, Jr., PhD, Program in Behavioral Neuroscience, Department of Psychology, 125 Nightingale Hall, Northeastern University, 360 Huntington Avenue, Boston, MA 02155, USA, E-mail: [email protected] Behavioural Pharmacology: June 2021 - Volume 32 - Issue 4 - p 295-307 doi: 10.1097/FBP.0000000000000616 Buy Metrics Abstract Pubertal male Syrian hamsters (Mesocricetus auratus) treated with anabolic/androgenic steroids (AASs) during adolescence (P27–P56) display a highly intense aggressive phenotype that shares many behavioral similarities with pathological aggression in youth. Anticonvulsant drugs like valproate that enhance the activity of the γ-aminobutyric acid (GABA) neural system in the brain have recently gained acceptance as a primary treatment for pathological aggression. This study examined whether valproate would selectively suppress adolescent AAS-induced aggressive behavior and whether GABA neural signaling through GABAA subtype receptors in the latero-anterior hypothalamus (LAH; an area of convergence for developmental and neuroplastic changes that underlie aggression in hamsters) modulate the aggression-suppressing effect of this anticonvulsant medication. Valproate (1.0–10.0 mg/kg, intraperitoneal) selectively suppressed the aggressive phenotype in a dose-dependent fashion, with the effective anti-aggressive effects beginning at 5 mg/kg, intraperitoneally. Microinfusion of the GABAA receptor antagonist bicuculline (7.0–700 ng) into the LAH reversed valproate’s suppression of AAS-induced aggression in a dose-dependent fashion. At the 70 ng dose of bicuculline, animals expressed the highly aggressive baseline phenotype normally observed in AAS-treated animals. These studies provide preclinical evidence that the anticonvulsant valproate selectively suppresses adolescent, AAS-induced aggression and that this suppression is modulated, in part, by GABA neural signaling within the LAH. Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.