Acute and subchronic effects of clozapine on licking in rats: tolerance to disruptive effects on number of licks, but no tolerance to rhythm slowing.

Abstract

In order to assess the effects of the atypical neuroleptic clozapine on orolingual competence in rats, tongue function was measured by quantitating the rhythm of tongue movements after acute (1.0, 3.0, 6.0 mg/kg) or subchronic intraperitoneal treatment (1.5, 3.0, 4.5 mg/kg, each dose for at least 7 days) with the drug. Thirsty rats were trained to lick water from a force-sensing disk by thrusting the tongue through a 12-mm-diameter hole to strike the horizontal disk located 5 mm below the hole. Number of licks in 2 min and rhythm of tongue movements (as determined by Fourier analysis of the force-time signal) were each dose dependently reduced in the acute dose-effect phase of the study. In the subchronic study number of licks exhibited tolerance, but the slowing of lick rhythm did not show tolerance. An acute dose range of the serotonin antagonist ritanserin (0.5, 1.0, 2.0, 4.0 mg/kg) was also studied in the same rats. Ritanserin had no effect on any of the measures of orolingual function. The clozapine result was replicated in a second study using younger, drug naive rats. The results for clozapine were contrasted with previous reports indicating that haloperidol has little effect on lick rhythm. Additional discussion evaluated the possible contribution of neurotransmitter receptors on motor neurons of the hypoglossal nucleus to the observed rhythm slowing induced by clozapine.