S(-)-nornicotine increases dopamine release in a calcium-dependent manner from superfused rat striatal slices.
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-dihydroxyphenylacetic acid (DOPAC) in the striatal superfusate and by an S(-)-nornicotine-induced increase in tritium overflow from striatal slices preloaded with [3H]DA. Low concentrations (0.01-1.0 microM) 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 microM) 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 overflow 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 microM S(-)-nornicotine was not different from that with no S(-)-nicotine, 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.
Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, University of Kentucky, Lexington 40536-0082.
L P
LP
Dwoskin
S T
ST
Buxton
A L
AL
Jewell
P A
PA
Crooks
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009538:Nicotine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011865:Radioisotope Dilution Technique; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D014316:Tritium
D014316:Tritium; D015102:3,4-Dihydroxyphenylacetic Acid; D009538:Nicotine; C005311:nornicotine; D002118:Calcium; D004298:Dopamine