Caffeine potentiates the discriminative-stimulus effects of nicotine in rats

Abstract

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.

Methylphenidate Enhances the Abuse-Related Behavioral Effects of Nicotine in Rats: Intravenous Self-Administration, Drug Discrimination, and Locomotor Cross-Sensitization

“…However, when coadministered with a subthreshold dose of nicotine (0.056 mg/kg), methylphenidate produced a dose-dependent increase in nicotine-appropriate responding, although the maximal effect of methylphenidate did not meet criteria used traditionally for declaring full substitution (ie X80% nicotine-appropriate responding). This augmentation in the effect of a low nicotine dose by methylphenidate is similar to results reported by Gasior et al (2002), who examined the discriminative stimulus effects of caffeine in nicotine-trained rats. In that report, rats were trained to discriminate nicotine (0.4 mg/kg) from saline, and dose-effect curves were generated for nicotine and caffeine, both alone and in combination with a subthreshold dose of nicotine (0.05 mg/kg).…”

“…In that report, rats were trained to discriminate nicotine (0.4 mg/kg) from saline, and dose-effect curves were generated for nicotine and caffeine, both alone and in combination with a subthreshold dose of nicotine (0.05 mg/kg). Similar to the present results, caffeine administered alone did not elicit nicotine-appropriate responding at any dose; however, when combined with a low dose of nicotine, caffeine dose-dependently generalized to the nicotine cue (Gasior et al, 2002). The fact that methylphenidate did not substitute for nicotine when given alone contrasts with other reports showing that the discriminative stimulus effects of other classical stimulant drugs overlap, at least partially, with the nicotine cue.…”

“…Caffeine, which augments extracellular dopamine levels, has been reported to potentiate the discriminative stimulus effect of a low nicotine dose (Gasior et al, 2002), suggesting that a similar mechanism may be implicated in the present drug discrimination results. However, evidence of a primary role for dopamine in mediating the nicotine cue is lacking, as selective dopamine antagonists generally fail to alter nicotine discrimination or attenuate nicotine discrimination only at doses that suppress response rates (Brioni et al, 1994;Corrigall and Coen, 1994;Le Foll et al, 2005).…”

Stimulus Properties of Nicotine, Amphetamine, and Chlordiazepoxide as Positive Features in a Pavlovian Appetitive Discrimination Task in Rats

“…Moreover, a dose below the ED 50 of caffeine in the operant study (10 mg/ kg; Young et al, 1998) evoked 100% amphetamine-appropriate responding in the present study. Caffeine does not substitute for 0.4 mg/kg nicotine in rats (Gasior et al, 2002;Rosecrans, 1989). However, caffeine partially substitutes for a low dose of nicotine (1 mg) delivered to humans in chewing gum (Duka et al, 1998).…”

“…There is considerable empirical evidence for such similarities in drug discrimination and in other behavioral paradigms. For example, caffeine pre-exposure and/or coadministration enhances the discriminative stimulus effects (ie shifts the dose-effect curve to the left) of nicotine (Gasior et al, 2000(Gasior et al, , 2002 and amphetamine (Schechter, 1977). Also, caffeine pre-exposure can enhance the psychomotor stimulant effects of nicotine and amphetamine in rats (Gasior et al, 2000;Palmatier et al, 2003).…”