Ca. Frye et al., BEHAVIORAL-EFFECTS OF 3-ALPHA-ANDROSTANEDIOL .1. MODULATION OF SEXUALRECEPTIVITY AND PROMOTION OF GABA-STIMULATED CHLORIDE FLUX, Behavioural brain research, 79(1-2), 1996, pp. 109-118
Pregnane neurosteroids may initiate sexual receptivity not only via ac
tions at intracellular receptors, but by affecting gamma-aminobutyric
acid (GABA) receptor complexes (GBRs). To investigate whether GBR-medi
ated actions of an androgenic neurosteroid 5 alpha-androstane-3 alpha,
17 beta-diol (3 alpha-androstanediol; 3 alpha-Diol) may influence the
expression of sexual behavior, ovariectomized (ovx) rats received dail
y injections of 3 alpha-Diol (0.6, 3.0, 6.0 and 7.5 mg/kg) or vehicle
(10% (v/v) ethanol in propylene glycol) at 10.00 h, and s.c. injection
s of estradiol-17 beta (E(2): 1 mu g/0.2 ml in 10% ethanol) at 13.00 h
and 19.00 h. Progesterone (P: 0.5, 1.0, 2.0 and 4.0 mg/kg) or sesame-
oil vehicle was given at 12.30 h on the day following two days of 3 al
pha-Diol and E(2) treatment. In Expt. 1, levels of sexual receptivity
were measured at 18.00-19.00 h, 56-57 h after the first injection of 3
alpha-Diol and 4 h after P or vehicle injection. 3 alpha-Androstanedi
ol (6.0 mg/kg) attenuated sexual behavior (lordosis quotient, lordosis
rating) and facilitated aggressive/rejection behaviors following 0.0,
1.0, 2.0 and 4.0 mg/kg P. The highest dosage of 3 alpha-Diol (7.5 mg/
kg) facilitated sexual behavior and inhibited aggression behaviors fol
lowing 0.0, 1.0, 2.0 and 4.0 mg/kg P. In Expt. 2, GABA-stimulated chlo
ride flux was greater in cortical synaptoneurosomes of animals that re
ceived hormone treatments associated with inhibited receptivity (E(2)P+3 alpha-Diol 3.0 mg/kg) than following treatments that facilitated r
eceptivity (E(2)+P and E(2)+P+3 alpha-Diol 7.5 mg/kg) or unreceptive o
vx animals. In Expt. 3, circulating concentrations of 3 alpha-Diol res
ulting from the 0.0, 3.0 and 7.5 mg/kg s.c. doses administered to E(2)
- and P-primed animals was measured by radioimmunoassay. Circulating l
evels of 3 alpha-Diol at the completion of behavioral testing were com
parable to those previously ascertained across the estrous cycle. Thes
e data indicate that 3 alpha-Diol influences the expression of E(2) an
d P-induced receptivity, and suggest that 3 alpha-Diol, like other neu
rosteroids, may exert its effects on sexual behavior by actions at GBR
s.