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Received for publication May 17, 2004.
Revised July 28, 2004.
Accepted for publication August 17, 2004.
-conotoxins on nicotine-stimulated [3H]dopamine release from rat striatal synaptosomes
Nicotine's action on the midbrain dopaminergic neurons is mediated by nicotinic acetylcholine receptors (nAChRs) that are present on the cell bodies and the terminals of these neurons. Previously, it was suggested that one of the nAChR subtypes located on striatal dopaminergic terminals may be an 
3
2 subtype, based on partial inhibition of nicotine-stimulated [3H]dopamine release by -conotoxin MII, a potent inhibitor of heterologously expressed 32 nAChRs. More recent studies indicated that -conotoxin MII also potently blocks 6-containing nAChRs. In the present study, we have examined the nAChR subtype(s) modulating [3H]dopamine release from striatal terminals by using novel -conotoxins that have 37-78 fold higher selectivity for 6- vs. 3-containing nAChRs. All of the peptides partially (20-35%) inhibit nicotine-stimulated [3H]dopamine release with IC50s consistent with those obtained with heterologously expressed rat 6-containing nicotinic acetylcholine receptors. These results, together with previous studies by others, further support the idea that 6-containing nicotinic receptors modulate nicotine-stimulated dopamine release from rat striatal synaptosomes.
Key words:
alpha-conotoxin MII, alpha-conotoxin PIA, dopamine release, nicotinic acetylcholine receptors, striatum, synaptosomes
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