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Vol. 301, Issue 2, 651-660, May 2002
Institute for Behavioral Genetics, University of Colorado, Boulder,
Colorado (S.R.G., K.L.M., J.C., M.J.M., A.C.C.); and Departments of
Biology and Psychiatry, University of Utah, Salt Lake City, Utah (M.M.)
The inhibition of uptake of [3H]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, [3H]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 [3H]dopamine in a form allowing vesicle-mediated release;
additionally, only the dopaminergic terminals have functional
presynaptic nAChRs that, when stimulated by nicotinic agonists, evoke
[3H]dopamine release. Agonist-stimulated
[3H]dopamine release was characterized from synaptosomes
prepared from four mouse brain regions.
-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 [3H]dopamine release was
detected in any brain region when the synaptosomes were prepared from
2 null mutant mice, which indicates that the
2 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 [3H]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.
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