HYPERACTIVITY INDUCED BY INJECTION OF DOPAMINE INTO THE ACCUMBENS NUCLEUS - ACTIONS AND INTERACTIONS OF NEUROLEPTIC, CHOLINOMIMETIC AND CHOLINOLYTIC AGENTS

The present studies determined whether the neuroleptic ability to antagonize hyperactivity caused by intra-accumbens injection of dopamine in the rat could be mimicked by cholinomimetics and reversed by cholinolytics. The dopamine response was antagonized by eserine (2.5 and 5 μg) and arecoline (10-40 μg), but methacholine (10-40 μg), acetylcholine (10-100 μg), carbachol (5 μg) and nicotine (10-40 μg) were either inactive or their effects were non-specific. The eserine response (5 μg) was reversed by peripherally administered atropine (5 mg/kg i.p.) but not by the nicotinic antagonist mecamylamine (5-40 μg). Systemically administered haloperidol (0.2-0.8 mg/kg i.p.) also reduced or abolished the dopamine response but this effect was not reversed by mecamylamine (10 mg/kg i.p.) or by atropine (1-5 mg/kg i.p.), procyclidine (10 mg/kg i.p.), orphenadrine (10 mg/kg i.p.) and dexetimide (1 mg/kg i.p.). These cholinolytics alone failed to modify the dopamine-induced hyperactivity. Thus, cholinomimetics may mimic the ability of neuroleptics to antagonize hyperactivity induced by dopamine from the nucleus accumbens, and the evidence would favour an interaction with the dopamine response via muscarinic cholinergic mechanisms, although a nicotinic involvement cannot be excluded. However, the results suggest that an enhanced cerebral cholinergic activity may not be essential for the neuroleptic inhibitory action, either in the nucleus accumbens or elsewhere. © 1979.