Nicotinic receptors modulating somatodendritic and terminal dopamine release differ pharmacologically

Ascending dopaminergic and noradrenergic neurons possess somatodendritic an d terminal nicotinic cholinoceptors in the rat. Each neuronal population ex presses mRNA for several types of nicotinic cholinoceptor subunit, includin g alpha 16 and beta 3. In superfused rat striatal synaptosomes, epibatidine evoked release of [H-3]dopamine with similar efficacy to ACh, whereas nico tine and cytisine were weaker (70 +/- 6% and 58 +/- 6%, respectively). The four agonists were equi-efficacious in evoking [H-3]noradrenaline release f rom hippocampal synaptosomes. Nicotine-evoked synaptosomal release was tetr odotoxin-insensitive. Somatodendritic nicotinic cholinoceptors on dopaminer gic neurons were studied using a dendrosomal [H-3]dopamine release assay an d 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 ni cotinic cholinoceptors located on dopaminergic neurons appear to differ pha rmacologically from those on striatal dopaminergic terminals and hippocampa l noradrenergic terminals. (C) 2000 Elsevier Science B.V. All rights reserv ed.