The effects of the nitric oxide synthase inhibitor 7-nitroindazole on the behaviour of mice after chronic ethanol administration.

Abstract

The effects of the nitric oxide synthase (NOS) inhibitor 7-nitroindazole (7-NI) on the behaviour of mice after chronic and acute ethanol administration were studied. Male albino mice received ethanol by inhalation for 25 days. The plus-maze and staircase tests were carried out with control, ethanol-intoxicated and ethanol-withdrawn mice (7.5 h after the end of ethanol administration). The administration of NOS inhibitor 7-NI [20.0 mg/kg, intraperitoneally (i.p.)] 60 min or 7.5 h before the plus-maze test induced an anxiolytic effect in control mice. Chronic ethanol administration induced an anxiolytic, and ethanol withdrawal an anxiogenic, effect in mice. The administration of 7-NI (20.0 mg/kg, i.p.) caused behavioural depression in ethanol-intoxicated mice, but had no effect on the behaviour of ethanol-withdrawn mice. 7-NI had no effect on the behaviour of control mice in the staircase test. Chronic ethanol administration increased, and ethanol withdrawal decreased, the locomotor activity of mice in the staircase test. Likewise, in the plus-maze test, administration of 7-NI caused behavioural depression in ethanol-intoxicated mice, but had no effect on the behaviour of ethanol-withdrawn mice. In additional experiments, vehicle or 7-NI (20.0-120.0 mg/kg, i.p.) were administered 30 min before ethanol (3.0 g/kg, i.p.). 7-NI dose-dependently increased the duration of ethanol-induced sleep and inhibited ethanol clearance. On the basis of these data we can propose that the NO system has no major role in behavioural changes caused by ethanol withdrawal. At the same time NOS inhibitors can cause synergistic CNS depression with ethanol.