Disinhibitory behavior and GABA(A) receptor function in serotonin-depletedadult 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 (GA BA(A)/BDZ-RC) and steroid hormones, e.g., testosterone. Here, we studied th e effect of gonadectomy on disinhibitory behavior in individually housed 5- HT-depleted rats and on GABA(A)/BDZ-RC function in vitro, in corticohippoca mpal synaptoneurosomes prepared from the brain of these animals. 5-HT deple tion by intracerebroventricular 5,7-dihydroxytryptamine (5,7-DHT)-induced d isinhibitory behavior in a shock-induced behavioral inhibition model (punis hed conflict model) 14 days after operation. Gonadectomy in connection with the 5-HT depletion reduced the disinhibitory behavior and testosterone sub stitution prevented this effect. Shock threshold and drinking motivation we re not affected by gonadectomy and/or 5-HT depletion. The relative epididym ides weight was increased in 5-HT-depleted as compared to sham-operated rat s. However, the serum concentrations of testosterone and the relative teste s weights were not different in 5-HT-depleted rats as compared to controls. GABA-induced (30, 100, 300 muM) Cl-36(-) -uptake into synaptoneurosomes wa s lower in 5,7-DHT + gonadectomized rats compared to the control group. Thi s effect was reversed by substitution with testosterone. These results demo nstrate that gonadectomy reduces disinhibitory behavior in 5-HT-depleted ra ts and that GABA(A)/BDZ-RC may be involved in this effect. (C) 2000 Elsevie r Science Inc. All rights reserved.