Nicotine and methamphetamine share discriminative stimulus effects.
BACKGROUND
Nicotine and methamphetamine are both abused in similar settings, sometimes together. Because there are known interactions between central nicotinic acetylcholine receptors and dopamine receptors, it is of interest to characterize the nature of the interaction of these two compounds in vivo.


METHODS
The purpose of this study was to characterize the extent to which these two compounds produce similar discriminative stimulus effects and to identify pharmacological mechanisms for their interaction. Male Sprague-Dawley rats were trained to discriminate methamphetamine or nicotine from saline. First, the ability of methamphetamine and nicotine to cross-substitute in rats trained to the other compound was tested. Subsequently, the ability of a dopamine antagonist (haloperidol) and a centrally acting nicotinic antagonist (mecamylamine) to block the discriminative stimulus effects of methamphetamine and nicotine were also tested.


RESULTS
Nicotine fully substituted in methamphetamine-trained rats, but methamphetamine only partially substituted in nicotine-trained rats. In nicotine-trained rats, mecamylamine fully antagonized the discriminative stimulus effects of nicotine, but haloperidol had no effect. The partial substitution of methamphetamine was partially attenuated by haloperidol, but not altered by mecamylamine. In methamphetamine-trained rats, mecamylamine failed to antagonize the discriminative stimulus effects of methamphetamine, but haloperidol fully blocked the methamphetamine cue. Mecamylamine blocked the ability of nicotine to substitute for methamphetamine, but haloperidol had no effect.


CONCLUSIONS
These results indicate that nicotine and methamphetamine share discriminative stimulus effects in some subjects and that the two compounds do not act at the same site, but produce their interaction indirectly. These findings suggest that these two compounds might be at least partially interchangeable in human users, and that there are potentially interesting pharmacological reasons for the commonly observed co-administration of nicotine and methamphetamine.
Gatch
Michael B
MB
Department of Pharmacology & Neuroscience, University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA. mgatch@hsc.unt.edu
Flores
Elva
E
Forster
Michael J
MJ
D000818:Animals; D002755:Choice Behavior / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects*; D008297:Male; D008464:Mecamylamine / Q000008:administration & dosage / Q000494:pharmacology; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011950:Receptors, Cholinergic / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000187:drug effects; D012965:Sodium Chloride / Q000008:administration & dosage / Q000494:pharmacology
D018733:Nicotinic Antagonists; D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; D011978:Receptors, Nicotinic; D008694:Methamphetamine; D012965:Sodium Chloride; D008464:Mecamylamine; D009538:Nicotine