The testosterone metabolite and neurosteroid 3alpha-androstanediol may mediate the effects of testosterone on conditioned place preference.
Testosterone (T) and pregnane neurosteroids can enhance conditioned place preference (CPP). The present experiment examined CPP produced by T and its androgenic metabolite dihydrotestosterone (DHT) and 3alpha-Androstanediol (3alpha-diol; an androstane neurosteroid). Administration of 3alpha-diol (>DHT>T) to intact male Long-Evans rats, 1.0 mg daily for six days, 30 min prior to exposure to the non-preferred side of the CPP chamber significantly increased preference for the non-preferred side of the chamber compared to that seen in home cage controls. Levels of circulating 3alpha-diol were increased significantly in 3alpha-diol>DHT>T-administered rats, compared to rats that had vehicle administered or androgen-administration discontinued. Androgen administration decreased seminal vesicle weight and intrahypothalamic androgen receptor (AR) binding compared to that seen in rats that had vehicle administered or androgen-administration discontinued. Testosterone, DHT, and 3alpha-diol decreased GABA-stimulated chloride influx in cortical synaptoneurosomes, and muscimol binding in the hippocampus compared to that seen in rats with vehicle administered or that had androgen-administration discontinued. These data indicate that administration of 3alpha-diol is more effective at enhancing CPP and increasing circulating 3alpha-diol levels than is DHT or T administration, and that all of the androgen regimens employed decreased peripheral and hypothalamic androgen receptor binding and cortical and hippocampal GABA(A) receptor function. Hence, whether the effects of 3 alpha-diol on CPP are mediated by differential actions at ARs or GABA(A) receptors in particular brain regions needs to be determined.
Frye
C A
CA
Department of Psychology, The University at Albany-SUNY, 1400 Washington Avenue, Albany, NY 12222, USA. cafrye@cnsunix.albany.edu
Park
D
D
Tanaka
M
M
Rosellini
R
R
Svare
B
B
D000728:Androgens / Q000097:blood; D015113:Androstane-3,17-diol / Q000494:pharmacology*; D000818:Animals; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism; D003216:Conditioning, Operant / Q000502:physiology*; D013196:Dihydrotestosterone / Q000494:pharmacology; D018755:GABA Agonists / Q000378:metabolism; D008297:Male; D009118:Muscimol / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011863:Radioimmunoassay; D051381:Rats; D011944:Receptors, Androgen / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D012669:Seminal Vesicles / Q000187:drug effects; D013739:Testosterone / Q000378:metabolism* / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000728:Androgens; D018118:Chloride Channels; D018755:GABA Agonists; D011944:Receptors, Androgen; D011963:Receptors, GABA-A; D013196:Dihydrotestosterone; D015113:Androstane-3,17-diol; D009118:Muscimol; D013739:Testosterone; D005680:gamma-Aminobutyric Acid