Scopolamine-induced convulsions in food given fasted mice: effects of clonidine and tizanidine

Abstract

We recently reported that scopolamine pretreated mice fasted for 48 h developed clonic convulsions soon after they were allowed to eat ad libidum. Pretreatment with MK-801, the non-competitive NMDA antagonist, decreased the incidence of these convulsions. We suggested that a possible scopolamine-induced glutamatergic hyperactivity could account for these convulsions. Using alpha(2)-agonists, clonidine, which has been shown to inhibit glutamate release, and tizanidine, the present study was performed to find some additional data for the role of glutamate in the underlying mechanism of scopolamine-induced convulsions in food given fasted mice. Animals fasted for 48 h and pretreated (i.p.) with saline, clonidine (0.05, 0.10, 1 mg/kg) or tizanidine (0.10, 0.15, 0.30, 0.45 mg/kg) were treated (i.p.) with either saline or scopolamine (3 mg/kg). Then 20 min later, they were allowed to eat ad libidum and were observed for 30 min for the incidence and onset of clonic convulsions. All doses of clonidine pretreatment completely suppressed (0%) scopolamine-induced clonic convulsions (75%). On the other hand, only 0.15 mg/kg tizanidine pretreatment significantly decreased (15%) the incidence of convulsions; however as well as 0.15 mg/kg, both 0.30 and 0.45 mg/kg tizanidine pretreatments significantly increased latency to the onset of convulsions. (C) 1999 Elsevier Science B.V. All rights reserved.