The testosterone metabolite and neurosteroid 3alpha-androstanediol may mediate the effects of testosterone on conditioned place preference

Psychoneuroendocrinology. 2001 Oct;26(7):731-50. doi: 10.1016/s0306-4530(01)00027-0.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Androgens / blood
  • Androstane-3,17-diol / pharmacology*
  • Animals
  • Chloride Channels / drug effects
  • Chloride Channels / metabolism
  • Conditioning, Operant / physiology*
  • Dihydrotestosterone / pharmacology
  • GABA Agonists / metabolism
  • Male
  • Muscimol / metabolism
  • Organ Size / drug effects
  • Radioimmunoassay
  • Rats
  • Receptors, Androgen / metabolism
  • Receptors, GABA-A / metabolism
  • Seminal Vesicles / drug effects
  • Testosterone / metabolism*
  • Testosterone / pharmacology*
  • gamma-Aminobutyric Acid / pharmacology


  • Androgens
  • Chloride Channels
  • GABA Agonists
  • Receptors, Androgen
  • Receptors, GABA-A
  • Dihydrotestosterone
  • Androstane-3,17-diol
  • Muscimol
  • Testosterone
  • gamma-Aminobutyric Acid