Disinhibitory behavior and GABA(A) receptor function in serotonin-depleted adult male rats are reduced by gonadectomy.

Impulsive and aggressive behaviors in, e.g., personality or substance abuse disorders in man and corresponding behaviors in rats may involve serotonin (5-HT), gamma-amino-butyric acid(A)/benzodiazepine receptor complexes (GABA(A)/BDZ-RC) and steroid hormones, e.g., testosterone. Here, we studied the effect of gonadectomy on disinhibitory behavior in individually housed 5-HT-depleted rats and on GABA(A)/BDZ-RC function in vitro, in corticohippocampal synaptoneurosomes prepared from the brain of these animals. 5-HT depletion by intracerebroventricular 5,7-dihydroxytryptamine (5,7-DHT)-induced disinhibitory behavior in a shock-induced behavioral inhibition model (punished conflict model) 14 days after operation. Gonadectomy in connection with the 5-HT depletion reduced the disinhibitory behavior and testosterone substitution prevented this effect. Shock threshold and drinking motivation were not affected by gonadectomy and/or 5-HT depletion. The relative epididymides weight was increased in 5-HT-depleted as compared to sham-operated rats. However, the serum concentrations of testosterone and the relative testes weights were not different in 5-HT-depleted rats as compared to controls. GABA-induced (30, 100, 300 microM) 36Cl(-)-uptake into synaptoneurosomes was lower in 5,7-DHT+gonadectomized rats compared to the control group. This effect was reversed by substitution with testosterone. These results demonstrate that gonadectomy reduces disinhibitory behavior in 5-HT-depleted rats and that GABA(A)/BDZ-RC may be involved in this effect.