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.
Fernández-Guasti
Alonso
A
Departamento de Farmacobiología Centro de Investigación y Estudios Avanzados del IPN, Col. Granjas Coapa Tlalpan, México. jfernand@mail.cinvestav.mx
Martínez-Mota
Lucía
L
D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage; D001007:Anxiety / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005442:Flumazenil / Q000494:pharmacology; D005485:Flutamide / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011944:Receptors, Androgen / Q000502:physiology*; D011963:Receptors, GABA-A / Q000502:physiology*; D013739:Testosterone / Q000008:administration & dosage / Q000378:metabolism*
D000726:Androgen Antagonists; D014151:Anti-Anxiety Agents; D018757:GABA Modulators; D011944:Receptors, Androgen; D011963:Receptors, GABA-A; D013739:Testosterone; D005442:Flumazenil; D005485:Flutamide