Caffeine potentiates the discriminative-stimulus effects of nicotine in rats.
BACKGROUND
Caffeine and nicotine are the main psychoactive ingredients of coffee and tobacco, respectively, with a high frequency of concurrent use in humans.


OBJECTIVE
The aim of the present study was to examine the interaction of caffeine and nicotine in rats trained to discriminate nicotine from saline.


METHODS
Two groups of male Sprague-Dawley rats ( n=8 per group) were trained to discriminate 0.4 mg/kg nicotine, SC, from saline under a fixed ratio schedule of food presentation. One group of rats was chronically exposed to caffeine (1.0 mg/ml) dissolved in their drinking water whereas the other group was exposed to tap water. Effects of IP injections of caffeine on nicotine-lever selection were subsequently examined. In separate groups of rats exposed to the same caffeine-drinking or water-drinking regimen, effects of caffeine pretreatment on nicotine plasma levels were evaluated.


RESULTS
Although caffeine (1.0-30.0 mg/kg) did not generalize to nicotine when administered alone, it markedly potentiated discriminative-stimulus effects of the threshold dose of nicotine (0.05 mg/kg) in both water- and caffeine-drinking rats. Nicotine plasma levels were, however, not affected by acute or chronic caffeine exposure.


CONCLUSIONS
Caffeine appears to enhance the discriminative-stimulus effects of the threshold dose of nicotine by a pharmacodynamic rather than a pharmacokinetic interaction. This suggests that caffeine consumption may be a contributing factor in the onset, maintenance of and relapse to tobacco dependence.
Gasior
Maciej
M
National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA. mgasior@mclean.harvard.edu
Jaszyna
Maria
M
Munzar
Patrik
P
Witkin
Jeffrey M
JM
Goldberg
Steven R
SR
D000818:Animals; D002110:Caffeine / Q000097:blood / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000097:blood / Q000494:pharmacology*; D004056:Differential Threshold; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005731:Ganglionic Stimulants / Q000008:administration & dosage* / Q000097:blood; D005795:Generalization, Stimulus / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000008:administration & dosage* / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule; D013805:Theobromine / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D000697:Central Nervous System Stimulants; D005731:Ganglionic Stimulants; D014665:Vasodilator Agents; D002110:Caffeine; D009538:Nicotine; D013806:Theophylline; D013805:Theobromine; C021183:1,7-dimethylxanthine