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.