Anxiolytic-like Actions of Testosterone in the Burying Behavior Test: Role of Androgen and GABA-benzodiazepine Receptors

The first objective of the present study was to explore if several androgens, including testosterone propionate (TP) and its reduced metabolites, 5alpha-androstan-3alpha, 17beta-diol (3alpha-androstanediol) and 5alpha-androstan-3alpha-ol-17-one (androsterone), produce an anxiolytic-like effect in the burying behavior paradigm. Additionally, the possible participation of androgen or GABA(A)-benzodiazepine receptors in the anxiolytic-like effect of TP was analyzed. Orchidectomized male rats were treated with four injections of TP (0.25, 0.50, 1.0 mg/rat), 3alpha-androstanediol or androsterone (0.5 and 1.0 mg/rat), and the cumulative burying (denoting anxiety levels) and burying behavior latency (reflecting reactivity) evaluated. Besides, a single injection (0.5 mg/rat, -30 m) of each androgen was also tested in castrated rats. Repeated treatment with TP (0.5 and 1.0 mg/rat), but not a single injection of this androgen, produced an anxiolytic-like effect without changes on reactivity. Neither repeated- nor single-treatment with 3alpha-androstanediol nor androsterone produced a reduction of anxiety-like behavior. For the experiment studying the TP mechanism of action, this androgen (0.5 mg/rat, four injections) was combined with an antagonist for androgen receptors, flutamide (50 mg/kg, SC, 7 injections), or with a benzodiazepine antagonist, flumazenil (15 mg/kg, IP, -30 m). Flutamide, but not flumazenil, blocked the anxiolytic-like effects produced by TP. Results are discussed on the basis of interaction of these steroids with androgen receptors or GABA(A)-benzodiazepine receptors.