Antagonism by cholinomimetic drugs of the turning induced by intrastriatal pirenzepine in mice

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Abstract
In order to investigate the behavioural effect of selective blockade of M1 muscarinic receptors in the forebrain, and to characterize a new model for the evaluation of muscarinic agonistic activity, the effect of intrastriatally injected pirenzepine was studied in mice. The direct injection of pirenzepine (0.01–1 μg/mouse) into the right striatum of conscious mice resulted in contralateral turning behaviour. When injected intraperitoneally (IP) 15 min before pirenzepine (1 μg), the muscarinic receptor agonists arecoline and pilocarpine (0.3–3 mg/kg), oxotremorine (0.003–0.03 mg/kg) and RS 86 (0.03–1 mg/kg) antagonized pirenzepine-induced turning, as did the choline-esterase inhibitor physostigmine (0.01–0.1 mg/kg) and the nootropic drug aniracetam (10–30 mg/kg). Haloperidol (0.03–0.3 mg/kg IP) weakly, but significantly, decreased the effect of pirenzepine, whereas (±) sulpiride (3–100 mg/kg) failed to affect it. Finally, (+)-amphetamine (0.1–3 mg/kg IP), citalopram (1–30 mg/kg IP) and muscimol (0.03–0.3 mg/kg IP) failed to modify pirenzepine-induced turning when administered prior to intrastriatal pirenzepine. These results suggest an involvement of M1 muscarinic receptors in rotational behaviour, and indicate that pirenzepine-induced turning may represent a new model for studying the central activity of cholinomimetic drugs.