Alcohol Dose-Dependently Enhances 3α-Androstanediol Formation in Frontal Cortex of Male Rats Concomitant with Aggression

ABSTRACT

Alcohol (EtOH) can enhance aggression in people and animal models. These effects are more salient in males than in females. Androgens, such as testosterone (T), may promote aggressive responding to EtOH. Effects of EtOH on androgens and aggression were examined in a resident-intruder paradigm. Gonadally-intact, or castrated (GDX), male rats were socially-isolated for 3 weeks and administered an acute dose of EtOH (2.0 g/kg) or saline (Experiment 1) or administered a dose-response regimen of EtOH (0.0, 0.5, 1.0, and 2.0 g/kg; Experiment 2). Cortical tissues were assessed for androgen concentrations and/or muscimol binding after receiving saline or EtOH. Compared to saline, acute EtOH administration in Experiment 1, enhanced aggression among intact rats and concomitantly enhanced formation of the T metabolite and neurosteroid, 3-androstanediol, (3-diol) in frontal cortex. T was also enhanced in cortex and circulation of intact but not GDX rats. Repeat testing in Experiment 2 revealed dose-dependent effects of EtOH to enhance aggression and cortical 3α -diol among both intact and GDX rats. EC50 for muscimol binding was lower for intact and EtOHadministered rats than for GDX or vehicle-administered rats, indicating that less GABA was needed to achieve halfmaximal binding. Together, these data suggest that 3α-diol enhancement may partly underlie EtOH’s effects on aggression, possibly via actions at GABA_A receptors.

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