Flutamide treatment induces anxiolytic-like behavior in adult castrated rats.
BACKGROUND
It has previously been speculated that the androgen receptor antagonist flutamide produces behavioral effects that are not mediated by androgen receptors. These earlier studies were performed in intact rodents and thus, flutamide may have interfered with endogenous testosterone produced by the testes. The main objective of the present study was to examine whether flutamide induces anxiolytic-like behavior in castrated rats.


METHODS
Male Wistar rats (8-9 weeks old) were castrated and thereafter, in the same operation, the rats received silastic capsules subcutaneously (sc) that were filled with dihydrotestosterone (DHT) or were left empty. Three weeks later, rats were sc administered flutamide 50 mg/kg/day or vehicle for seven days. Four hours after the last injection, anxiolytic-like behavior was studied in a modified Vogel's drinking conflict model. In a separate experiment, shock threshold and drinking motivation were estimated.


RESULTS
Flutamide induced anxiolytic-like behavior in castrated rats irrespective of administration of DHT. Treatment with DHT alone did not induce a significant behavioral effect. Shock threshold and drinking motivation were not affected by flutamide and/or DHT treatment.


CONCLUSIONS
This study demonstrates that flutamide induces anxiolytic-like behavior in a modified Vogel's conflict model in castrated rats, which indicates that flutamide has anxiolytic-like properties that are not dependent on testes-produced testosterone.
Addiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, PO Box 410, SE-405 30 Gothenburg, Sweden. anders.svensson@neuro.gu.se.
Anders I
AI
Svensson
D000726:Androgen Antagonists / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects*; D013196:Dihydrotestosterone / Q000494:pharmacology; D004326:Drinking / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions; D004597:Electroshock; D005485:Flutamide / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008297:Male; D009042:Motivation / Q000187:drug effects / Q000502:physiology; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000378:metabolism*
D000726:Androgen Antagonists; D014151:Anti-Anxiety Agents; D013196:Dihydrotestosterone; D013739:Testosterone; D005485:Flutamide