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Differences in the action of the ergot derivatives bromocriptine lisuride and lsd on the acetylcholine turnover in striatum and the mesolimbic structures of rat brain


, : Differences in the action of the ergot derivatives bromocriptine lisuride and lsd on the acetylcholine turnover in striatum and the mesolimbic structures of rat brain. Biogenic Amines 2(4): 305-316

The effects of the ergot derivatives bromocriptine, lisuride and LSD on the acetylcholine turnover in striatum and mesolimbic structures of rat brain were estimated by using the finite differences method. The acetylcholine and choline contents were measured radioenzymatically. After intravenous pulse injection of [3H] choline the radioactivity of both [3H] acetylcholine and [3H] choline was measured in the above brain areas. After bromocriptine administration (30 mg/kg i.p.) the acetylcholine turnover was decreased in striatum, nucleus accumbens and olfactory tubercle, respectively. Both pretreatment with lisuride (0.4 mg/kg i.p.) and LSD (0.1 mg/kg i.p.) led to an increase in the acetylcholine turnover in the mesolimbic nuclei, whereas the striatum was unaffected by these drugs. The effects of bromocriptine on the rate of cholinergic activity provides further evidence for an inhibitory dopaminergic modulation of cholinergic interneurons in the striatum and in the mesolimbic nuclei. The effects of lisuride and LSD on cholinergic neurons in the mesolimbic areas appear to be mediated through a preferential action on dopaminergic and serotoninergic autoregulatory processes in the ventral tegmental area and in the raphe nuclei, respectively, leading to an disinhibition of cholinergic neurons. The lack of modification of the acetylcholine turnover in the striatum after both drugs refers to several pharmacological and functional differences between the nigrostriatal and mesolimbic dopamine systems. The differential response of striatal and mesolimbic dopamine systems to various drugs appears to be due to differences in the modulation of dopamine synthesis and firing rate of dopamine neurons consequent to differences in autoregulatory processes and negative feed back mechanisms.

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