The effect of psychoactive drugs on plasma corticosterone levels and behaviour in the bulbectomised rat

Abstract

Bilateral olfactory bulbectomy (OB) in the rat produces a rise in circulating 11-hydroxycorticosterone (11-OHCS) to intermediate levels (40–50 μg/100 ml plasma). Following footshock extreme corticosterone elevation occurs (65–80 μg/100 ml plasma). Bulbectomy also produces behavioural changes which include hyper-reactivity and an acquisition deficit in a step-down passive avoidance test. Treatment of the bulbectomised rat with amitriptyline (5 and 10 mg/kg), mianserin (5 and 10 mg/kg) and viloxazine (2 and 5 mg/kg) administered IP for at least 7 days corrected the acquisition deficit, reduced the hyper-reactivity and the elevated corticosterone levels in a reproducible manner. This reduction in 11-OHCS concentrations occurred in bulbectomised rats with and without footshock. In contrast, the antidepressant drugs did not produce these changes in sham-operated controls (SO). The central stimulant, amphetamine (1 and 3 mg/kg/day for 7 days, IP), increased 11-OHCS concentrations in unstressed OB and SO rats. There was no further elevation in the 11-OHCS concentrations of stressed rats of both OB and SO groups. This drug further impaired the acquisition of both OB and SO rats and increased the reactivity scoring of both groups. The major tranquillizer, chlorpromazine (1 and 3 mg/kg IP for 7 days), reduced plasma 11-OHCS levels and the hyperreactivity of both OB and SO groups. It did not reduce the acquisition deficit exhibited by the OB rats. Chlordiazepoxide (5 and 15 mg/kg IP for 7 days), had a profile similar to that of chlorpromazine except that it impaired acquisition in the SO group. Thus using the techniques described above it is possible to separate the antidepressants from other major classes of psychotropic drugs.