Characterization of nicotinic agonist-induced [(3)H]dopamine release from synaptosomes prepared from four mouse brain...

The inhibition of uptake of [(3)H]dopamine into synaptosomes prepared from four mouse brain regions was investigated. The inhibition curves demonstrated that in three regions, striatum, nucleus accumbens, and olfactory tubercle, [(3)H]dopamine was taken up exclusively by dopaminergic terminals. In frontal cortex, however, only a portion of the uptake was into dopaminergic terminals, with a larger amount taken up by noradrenergic terminals, and another small portion by serotonergic terminals. Release studies in frontal cortex indicated that in this region only dopaminergic and noradrenergic terminals are capable of packaging [(3)H]dopamine in a form allowing vesicle-mediated release; additionally, only the dopaminergic terminals have functional presynaptic nAChRs that, when stimulated by nicotinic agonists, evoke [(3)H]dopamine release. Agonist-stimulated [(3)H]dopamine release was characterized from synaptosomes prepared from four mouse brain regions. alpha-Conotoxin MII was a partial inhibitor of dopamine release in all of the brain regions, which suggests that a minimum of two nicotinic cholinergic receptors (nAChRs) are expressed in the nerve terminals of all four brain regions. No nicotine-induced [(3)H]dopamine release was detected in any brain region when the synaptosomes were prepared from beta2 null mutant mice, which indicates that the beta2 subunit is required for all nAChRs mediating this release. Dose-response curves were constructed for seven agonists in each of the brain regions. The pharmacological properties of synaptosomal [(3)H]dopamine release appear similar across the four brain regions. The results suggest that all four regions express the same nAChRs, although subtle regional differences may exist.