Presynaptic nicotinic receptors modulating dopamine release in the rat striatum

The modulation of striatal dopamine release by presynaptic nicotinic acetyl chorine receptors is well documented for both synaptosomes and slices. Beca use the latter retain local anatomical integrity, we have compared [H-3]dop amine release evoked by the nicotinic receptor agonists (-)-nicotine and (/-)-anatoxin-a from striatal synaptosome and slice preparations in parallel . At higher agonist concentrations, mecamylamine-sensitive [H-3]dopamine re lease was greater from slices, indicative of an additional component, and t his increase was abolished by glutamate receptor antagonists. To begin to e xamine the localisation of specific nicotinic acetylchorine receptor subtyp es in the striatum, immunogold electron microscopy was undertaken with the beta 2-specific monoclonal antibody 270. In striatal sections, gold particl es were associated with symmetric synapses (dopaminergic) but were absent f rom asymmetric synapses (glutamatergic). Surface labelling of striatal syna ptosomes with gold particles was also demonstrated. Taken together, these r esults are consistent with dopamine release mediated by beta 2-containing n icotinic acetylcholine receptors on dopamine terminals, while non-beta 2-co ntaining nicotinic acetylcholine receptors may enhance dopamine release ind irectly by releasing glutamate from neighbouring terminals. (C) 2000 Elsevi er Science B.V. All rights reserved.