The effect of manipulation of cholinergic mechanisms on turning behaviour in mice with unilateral destruction of the nigro-neostriatal dopaminergic system

Abstract

The effect of systemically administered centrally-acting cholinergic and anticholinergic drugs on circling behaviour induced by the dopamine agonists apormorphone and amphetamine in mice with unilateral 6-hydroxydopamine lesions of nigro-neostriatal dopamine terminals has been studied. The anticholinergic drugs, scopolamine and benztropine, both caused circling towards the side of the lesion when administered alone to this animal model. Scopolamine and benztropine also significantly potentiated the ipsiversive circling behaviour induced by amphetamine, but had no consistent effect on apomorphine-induced contraversive turning. The cholinergic agents, physostigmine, arecoline and pilocarpine, produced no circling activity when given alone, but depressed the rates of circling induced by both amphetamine and apomorphine in these lesioned mice. The peripherally-acting drugs, methylscopolamine or neostigmine. neither produced any motor effects by themselves nor modified the circling behaviour induced by either amphetamine or apomorphine. Methylscopolamine had no effect on the inhibition of the amphetamine- or apomorphine-induced circling response by physostigmine. Pretreatment of the lesioned mice with either α-methyl- p-tyrosine or haloperidol abolished the circling response induced by amphetamine or scopolamine. The possible mechanisms and sites of interaction of the cholinergic and anticholinergic drugs with the nigro-neostriatal dopaminergic pathway are discussed.