Nicotinic agonists elicit the release of dopamine from striatal synaptosomes by acting on presynaptic nicotinic acetylcholine receptors (nAChRs) on dopamine nerve terminals. Both alpha 3 beta 2* and alpha 4 beta 2 nAChR subtypes (but not alpha 7* nAChRs) have been implicated. Here, we compared nAChR-evoked [H-3]dopamine release from rat striatal synaptosome and slice preparations by using the nicotinic agonist anatoxin-a. In the more integral slice preparation, the concentration-response curve for anatoxin-a-evoked [H-3]dopamine release was best fitted to a two-site model, giving EC50 values of 241 nM and 5.1 mu M, whereas only the higher-affinity component was observed in synaptosome preparations (EC50 = 134 nM). Responses to a high concentration of anatoxin-a (25 mu M) in slices (but not in synaptosomes) were partially blocked by ionotropic glutamate receptor antagonists (kynurenic acid, 6,7-dinitroquinoxaline-2,3-dione) and by alpha 7*-selective nAChR antagonists (alpha-bungarotoxin, alpha-conotoxin-ImI, methyllycaconitine) in a nonadditive manner. In contrast, the alpha 3 beta 2-selective nAChR antagonist alpha-conotoxin-MII partially inhibited [H-3]dopamine release from both slice and synaptosome preparations, stimulated with both low (1 mu M) and high (25 mu M) concentrations of anatoxin-a. Antagonism by alpha-conotoxin-MII was additive with that of alpha 7*-selective antagonists. These data support a model in which alpha 7* nAChRs on striatal glutamate terminals elicit glutamate release, which in turn acts at ionotropic glutamate receptors on dopamine terminals to stimulate dopamine release. In addition, non-alpha 7* nAChRs on dopamine terminals also stimulate dopamine release. These observations have implications for the complex cholinergic modulation of inputs onto the major efferent neurons of the striatum.
|Number of pages||7|
|Publication status||Published - 2000|