Anti-serotonin action in combination with noradrenaline-stimulating action is important for inhibiting muricide in midbrain raphe-lesioned rats

Abstract

The present study was designed to examine the possible involvement of both an anti-serotonin action and a catecholamine-stimulating action in the mechanism of the inhibition of the muricide in rats with lesions of the midbrain raphe. Serotonin antagonists, such as cyproheptadine (10 mg/kg), cinanserin (10 mg/kg) and pirenperone (1 mg/kg), given alone showed little suppression of muricide in rats with raphe lesions, although the first two drugs were inhibitory at very large doses. Methamphetamine showed no inhibition of muricide at 0.32 mg/kg (i.p.), but exerted a marked inhibition of muricide when combined with the above serotonin antagonists. In addition, the dose-response curve for cyproheptadine and cinanserin was shifted markedly to the left when combined with l-threo-3,4-dihydroxyphenylserine ( l-threo-DOPS) (100 mg/kg i.p.), but not with lisuride (0.32 mg/kg i.p.). Similarly, pirenperone produced a marked inhibition of muricide at doses of 0.32–1.8 mg/kg (i.p.) when combined with l-threo-DOPS, but not when combined with lisuride. These results suggest that the combination of an anti-serotonin action with noradrenergic activation is important for inhibiting muricide, at least in rats with raphe lesions. A similar mechanism also seems to be valid for the anti-muricidal effect of antidepressant drugs.