D. Bitran et al., CHRONIC ANABOLIC-ANDROGENIC STEROID TREATMENT AFFECTS BRAIN GABA(A) RECEPTOR-GATED CHLORIDE-ION TRANSPORT, Life sciences, 58(7), 1996, pp. 573-583
Citations number
39
Categorie Soggetti
Biology,"Medicine, Research & Experimental","Pharmacology & Pharmacy
Previous research in this laboratory has shown that chronic treatment
of adult male rats with an anabolic-androgenic steroid (AAS) produced
anxiolytic behavior and increased the functional response of cortical
gamma-aminobutyric acid(A) (GABA(A)) receptors. The experiments report
ed here were aimed at further characterizing the effect of chronic AAS
exposure on cerebral cortical GABA(A) receptors. Adult male rats were
injected with dianabol (1,4-androstadien-17 alpha-methyl-17 beta-ol-3
-one; 10 mg/kg/day, SC) for 4 weeks. A significant decrease in ventral
prostate gland weight was found after 2 weeks of dianabol, and return
ed to control levels 3 and 10 days after steroid discontinuation. Test
icular weights decreased throughout the treatment period but reached s
tatistical significance only during the withdrawal period. Serum 3 alp
ha-androstanediol level was marginally increased after 2 weeks of dian
abol injection, and was significantly decreased at 3 and 10 days after
withdrawal. GABA-stimulated (36)chloride (Cl-) influx in cortical syn
aptoneurosomes was increased in animals treated with dianabol for 2 an
d 4 weeks, and remained elevated 3 days after dianabol withdrawal, ret
urning to control levels at withdrawal day 10. The increase in recepto
r efficacy was associated with a transient increase in receptor sensit
ivity (inverse of EC(50)), apparent after 2 weeks of AAS treatment and
at withdrawal day 3. In a follow-up experiment, metabolites of dianab
ol were tested for the in vitro efficacy in potentiating GABA-stimulat
ed Cl- transport. Only 3 alpha-androstanediol and androsterone were fo
und to have potent stimulatory effects. The 3 beta-reduced metabolites
were inactive, as were metabolites that contained a methyl group at t
he 17 alpha position. These results point to significant facilitative
effects of dianabol treatment on brain GABA(A) receptors via the metab
olic formation of neuroactive steroids.