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S (‐)‐Nornicotine Increases Dopamine Release in a Calcium‐Dependent Manner from Superfused Rat Striatal Slices
Author(s) -
Dwoskin Linda P.,
Buxton Susan T.,
Jewell Ann L.,
Crooks Peter A.
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb03502.x
Subject(s) - nornicotine , chemistry , nicotine , calcium , dopamine , biophysics , endocrinology , medicine , biology , alkaloid , stereochemistry , organic chemistry
The present study demonstrates that S (‐)‐nornicotine evoked a concentration‐dependent increase in dopamine (DA) release from superfused rat striatal slices. The increase in DA release was indicated by an S (‐)‐nornicotine‐induced overflow of endogenous 3,4‐dihydroxyphenyl‐acetic acid (DOPAC) in the striatal superfusate and by an S (‐)‐nornicotine‐induced increase in tritium overflow from striatal slices preloaded with [ 3 H]DA. Low concentrations (0.01–1.0 μ M ) of S (‐)‐nornicotine, which did not evoke endogenous DOPAC overflow, also were unable to modulate electrically evoked DOPAC overflow. The increase in DOPAC overflow induced by S (‐)‐nornicotine was compared with that produced by S (‐)‐nicotine. Comparing equimolar concentrations (0.1‐100 μ M ) of S (‐)‐nornicotine and S (‐)‐nicotine, superfusion with S (‐)‐nornicotine resulted in a significantly greater DOPAC overflow. In contrast to the effect of S (‐)‐nicotine, S (‐)‐nornicotine evoked a sustained increase in DOPAC over‐flow for the entire period of S (‐)‐nornicotine exposure. Furthermore, DOPAC overflow evoked by S (‐)‐nornicotine in control Krebs buffer was inhibited by superfusion with a low‐calcium buffer. Moreover, in the low‐calcium buffer, DOPAC overflow induced by 30 and 100 μ M S (‐)‐nornicotine was not different from that with no S (‐)‐nornicotine. The results indicate that S (‐)‐nornicotine, a constituent of tobacco products and a known metabolite of S (‐)‐nicotine, increases DA release in a calcium‐dependent manner in superfused rat striatal slices. It is interesting that unlike S (‐)‐nicotine, there does not appear to be desensitization to this effect of S (‐)‐nornicotine.