Nicotinic receptors modulating somatodendritic and terminal dopamine release differ pharmacologically

Ascending dopaminergic and noradrenergic neurons possess somatodendritic and terminal nicotinic cholinoceptors in the rat. Each neuronal population expresses mRNA for several types of nicotinic cholinoceptor subunit, including alpha6 and beta3. In superfused rat striatal synaptosomes, epibatidine evoked release of [3H]dopamine with similar efficacy to ACh, whereas nicotine and cytisine were weaker (70+/-6% and 58+/-6%, respectively). The four agonists were equi-efficacious in evoking [3H]noradrenaline release from hippocampal synaptosomes. Nicotine-evoked synaptosomal release was tetrodotoxin-insensitive. Somatodendritic nicotinic cholinoceptors on dopaminergic neurons were studied using a dendrosomal [3H]dopamine release assay and also in locomotor activity tests. In both assays, nicotine appeared more efficacious than epibatidine. Furthermore, with repeated nicotine exposure, the acute locomotor stimulant response to nicotine increased, whereas the epibatidine response became undetectable. In conclusion, somatodendritic nicotinic cholinoceptors located on dopaminergic neurons appear to differ pharmacologically from those on striatal dopaminergic terminals and hippocampal noradrenergic terminals.