Effects of mecamylamine, nicotine, atropine and physostigmine on the phencyclidine-induced behavioral toxicity

Abstract

Phencyclidine (PCP) has multifaceted actions on the cholinergic functions, including interaction with the central and peripheral cholinergic receptors. Therefore, to evaluate the possible involvement of the nicotinic and muscarinic acetylcholine (ACh) receptors during the behavioral toxicity of PCP, influence of various cholinergic modifiers on the PCP-induced behavioral effects in male Swiss mice was studied. PCP-induced (45 μmol/kg, IP) behavioral toxicity (circular movements, side-to-side head movements, and hyperactivity leading to convulsions) was blocked by pretreating the animals with secondary- or tertiaryamino-cholinergic modifiers, mecamylamine (ME; 14.9 and 29.9 μmol/kg), nicotine (NI; 12.3 and 30.8 μmol/kg) and physostigmine (PH; 0.16 and 0.31 μmol/kg). NI at 1.5 μmol/kg significantly potentiated the PCP-induced convulsions. Atropine (AT; 14.4 and 28.8 μmol/kg) pretreatments shortened the onset of circular movements. The locomotor activity of PCP (16.4 μmol/kg) was blocked by ME, NI, and PH. AT at 7.2 μmol/kg significantly potentiated the PCP-locomotion by 62%. These observations indicated that the behavioral actions of PCP, at least in part, are mediated by the central nicotinic and muscarinic ACh receptors. The involvement of cholinergic receptors in conjunction with the dopaminergic actions of PCP during these behaviors also has been discussed.