Effects of caffeine on persistence and reinstatement of nicotine-seeking behavior in rats: interaction with nicotine-associated cues

Abstract

Caffeine and nicotine are the most commonly co-used psychostimulants. However, it is still unclear whether caffeine exposure enhances nicotine-seeking behavior. The present study examined the effects of caffeine on nicotine-seeking in rats trained to self-administer nicotine with and without presession administration of caffeine. Male Sprague-Dawley rats were trained to intravenously self-administer nicotine (0.03 mg/kg/infusion, freebase) on a fixed ratio 5 schedule of reinforcement and associate a stimulus cue with each nicotine administration. Five minutes before the sessions, the rats received an intraperitoneal administration of caffeine (5 mg/kg). Extinction tests were conducted under four conditions: presession caffeine administration, response-contingent presentation of nicotine cues, neither condition, or both conditions. Reinstatement tests were conducted after responding was extinguished by withholding presession caffeine, nicotine, and its cues. A separate group of rats trained without presession caffeine exposure was also subjected to the reinstatement tests. In the rats trained with presession caffeine exposure, continued caffeine administration sustained nicotine-seeking responses and interacted with nicotine cues to significantly delay the extinction of nicotine-seeking behavior. Readministration of caffeine after extinction effectively reinstated nicotine-seeking behavior. In caffeine-naive rats, caffeine administration did not reinstate extinguished nicotine-seeking behavior but significantly potentiated the cue-induced reinstatement of nicotine-seeking. These data demonstrate that caffeine administration sustained and reinstated nicotine-seeking behavior, possibly via its acquired discriminative-stimulus properties predictive of nicotine availability. These findings suggest that smokers who attempt to quit may benefit from stopping caffeine consumption.