Research report
Behavioral effects of 3a-androstanediol II: Hypothalamic and preoptic area actions via a GABAergic mechanism

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Abstract

We investigated whether 5a-androstane-3α,17fi-diol (3α-androstanediol; 3α-Diol), a neurosteroid whose effects are primarily inhibitory to sexual behavior, may act through interactions with y-aminobutyric acid (GABA) receptor complexes (GBRs) in the medial basal hypothalamus (MBH) and the preoptic area (POA). In Experiment (Exp.) 1, ovariectomized (ovx) rats were implanted with bilateral guide cannulae aimed above the MBH and were later treated with 17/3-estradiol (E2, 2 injections of 1 μg/0.2 ml in 10% ethanol) and either 3α-Diol (3.0 mg/kg, s.c.) or vehicle. Progesterone (0.5 mg, s.c.) was given 24 h after the first E2 injection and a pre-test for lordosis responsiveness was carried out 4 h later. The GABAA agonist, muscimol (50 ng), then was infused into the MBH and rats were tested 10, 30 and 60 min later. Muscimol infusion facilitated lordosis behavior in vehicle-treated controls, but 3α-Diol-treated animals failed to show this facilitation. To ascertain whether 3a-Diol would also prevent muscimol's action in the POA, a site in which muscimol inhibits, rather than facilitates, sexual receptivity, ovx animals in Exp. 2 were implanted with bilateral guide cannulae aimed above the POA and were treated with E2, 3α-Diol, and P and infused and tested as in Exp. 1. Muscimol and 3a-Diol each significantly inhibited receptivity; when they were combined, the inhibition was more pronounced. In Exp. 3, POA infusions of the GABAA antagonist, bicuculline, counteracted muscimol's and 3α-Diol's inhibition of sexual behavior. In Exp. 4, in vitro treatment of POA and MBH membrane fractions with 3α-Diol (30 μM) enhanced maximal [3H]muscimol binding without altering the affinity of the binding sites for the agonist. These data suggest that 3α-Diol inhibits E2 and progest-ininduced lordosis behavior via actions at the GBR in both the MBH and POA.

Keywords

Neurosteroid
Neuroactive steroid
Steroid mechanism
Non-genomic
Progestin
Lordosis
Proceptivity
Aggression

Cited by (0)

1

Present address: National Center for Post Traumatic Stress Disorder, DVA Medical Center, 150 South Huntington Avenue, Boston, MA 02130, USA.

2

Present address: Program in Neuroscience, University of Rochester, Rochester, NY 14627, USA.