Effect of nicotine on dopaminergic-cholinergic interaction in the striatum

We have investigated the effect of nicotinic receptor stimulation on acetylcholine (ACh) release measured by radioassay in rat striatal slices. Since the release of ACh in the striatum is tonically inhibited by endogenous dopamine and nicotine enhances the release of dopamine, we studied the release of ACh when the dopaminergic input was impaired. We used chemical denervation (6-hydroxydopamine pretreatment) or D2-receptor-blockade by sulpiride to remove the dopaminergic control of the cholinergic neurons. In our experiments nicotine failed to increase ACh release from striatal slices taken from rats whose dopaminergic-cholinergic interaction was not impaired but it enhanced the release of ACh from slices dissected from 6-hydroxydopamine pretreated rats or in the presence of sulpiride. Our results provide neurochemical evidence for the existence of nicotinic receptors on striatal cholinergic interneurons. Since the spontaneous release of ACh enhanced by nicotine was inhibited by tetrodotoxin it seems very likely that (-)-nicotine acts on the somatodendritic part of cholinergic interneurons.