Dopamine modulation of acetylcholine release from the guinea-pig brain

The effect of dopamine (DA) and apomorphine (Apo) on acetylcholine (ACh) release from guinea-pig brain was investigated (i) in superfused slices of cerebral cortex, caudate nucleus, tuberculum olfactorium, brain stem and (ii) in unrestrained, unanaesthetized animals, provided with epidural parietal cups. DA reduced the ACh release only from slices of caudate nucleus, whereas Apo was also effective in the cerebral cortex. DA and Apo inhibition in caudate nucleus was antagonized by spiroperidol. The injection of DA (1.5 and 5 micromoles) into the cerebral ventricles (i.c.v.) caused a late, moderate behavioural stimulation and enhanced ACh outflow from the parietal cortex. The injection of Apo, either i.c.v. or i.p., promptly elicited similar effects. Spiroperidol 0.5--2 mg/kg i.p. counteracted the behavioural stimulation by Apo and amphetamine, but unexpectedly enhanced the cortical ACh outflow, leaving unaffected the cholinergic responses to Apo and Amphetamine. These results show that DA directly hinders ACh release from the striatal cholinergic structures surviving in vitro, via classical neuroleptic-sensitive receptors. On the other hand, the enhanced cortical ACh outflow caused by DA and DA-mimetic drugs in the unanaesthetized animals is suggestive of a disinhibition of the corticopetal cholinergic neurones, via neuroleptic-insensitive mechanisms. Hence, the 'paradoxical' effect of spiroperidol might represent the consequence of the increased activity of nigral DA cells with collaterals possibly involved in the control of the ascending cholinergic pathways.