title: Intrahippocampal administration of an androgen receptor antagonist, flutamide, can increase anxiety-like behavior in intact and DHT-replaced male rats.
abstract: Testosterone (T) and its 5alpha-reduced metabolite, dihydrotestosterone (DHT), can decrease anxiety-like behavior; however, the mechanisms underlying these effects have not been established. First, we hypothesized that if T reduces anxiety-like behavior through actions of its 5alpha-reduced metabolite, DHT, then gonadectomy (GDX) would increase anxiety-like behavior, an effect which would be reversed by systemic administration of DHT. Second, we hypothesized that if T and DHT reduce anxiety-like behavior in part through actions at intracellular androgen receptors in the hippocampus, then administration of an androgen receptor antagonist, flutamide, directly to the hippocampus should increase anxiety-like behavior of intact and DHT-replaced, but not GDX, male rats. Inserts that were empty or contained flutamide were applied directly to the dorsal hippocampus of intact, GDX, or GDX and DHT-replaced rats 2 h prior to testing in the open field, elevated plus maze, or defensive freezing tasks. GDX rats exhibited significantly more anxiety-like behaviors than intact or DHT-replaced rats. Intact and DHT-replaced rats administered flutamide to the hippocampus showed significantly more anxiety-like behavior than did intact and DHT-replaced controls. However, flutamide alone did not increase anxiety-like behavior of GDX rats. Together, these findings suggest that androgens can decrease anxiety-like behavior of male rats in part through DHT's actions at androgen receptors in the hippocampus.
authors.affiliation: Department of Biological Sciences, The University at Albany-SUNY, 1400 Washington Avenue, Albany, NY 12222, USA.
authors.forename: Kassandra L
authors.initials: KL
authors.lastname: Edinger
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Frye
mesh_terms: D000726:Androgen Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D059002:Androgen Receptor Antagonists; D000818:Animals; D001007:Anxiety / Q000523:psychology*; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004343:Drug Implants; D005485:Flutamide / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000502:physiology*; D020249:Hormone Replacement Therapy; D008297:Male; D009919:Orchiectomy; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D004343:Drug Implants; D013196:Dihydrotestosterone; D005485:Flutamide