Antagonism of diazepam against central anticholinergic drug-induced hyperactivity in mice: Involvement of a GABA mechanism

Abstract

In mice tested for 30 min in photometer activity boxes , an increased activity (hyperactivity) was observed after intraperitoneal administration of benztropine (8 mg/kg), scopolamine (2 mg/kg), atropine (24 mg/kg) and trihexyphenidyl (8 mg/kg). Such hyperactivity was reduced or suppressed by diazepam (0.5, 1 or 2 mg/kg i.p.). At these doses no reduction of spontaneous activity was found with diazepam. Picrotoxin (1 or 2 mg/kg s.c.), but neither thiosemicarbazide (4–64 mg/kg s.c.) nor strychnine (0.25 and 0.5 mg/kg s.c.) antagonized the inhibitory effects of diazepam on each anticholinergic drug-induced hyperactivity. Picrotoxin (0.5, 1 or 2 mg/kg) did not modify the decreased spontaneous activity elicited by diazepam (4 mg/kg). These results suggest that diazepam may exert its antagonistic effect on the hyperactivity induced by anticholinergic drugs through a link with the γ-aminobutryic acid (GABA) system and more precisely through direct stimulation of GABA receptors. However, since picrotoxin did not modify the reduction of the spontaneous activity induced by diazepam, one can assume that diazepam-elicited decreased activity does not involve a GABA-ergic component and furthermore does not fully determine the effects of this benzodiazepine against the hyperactivity induced by anticholinergic drugs.