1. ¹Department of Psychology, College of Arts and Sciences, University of Kentucky, Lexington, KY, USA
2. ²Department of Behavioral Science, College of Medicine, University of Kentucky, Lexington, KY, USA
3. ³Department of Psychiatry, College of Medicine, University of Kentucky, Lexington, KY, USA

Correspondence: Professor MT Bardo, Department of Psychology, College of Arts and Sciences, University of Kentucky, BBSRB, Room 253, Lexington, KY 40536-0509, USA. Tel: +1 859 257 6456; Fax: +1 859 257 3235; E-mail: mbardo@uky.edu

Received 22 February 2007; Revised 25 April 2007; Accepted 14 May 2007; Published online 20 June 2007.

Abstract

Stimulant drugs, including D-amphetamine, cocaine, and methylphenidate, increase cigarette smoking in controlled human laboratory experiments. Although the mechanism(s) underlying this effect are unknown, it is possible that stimulants may enhance directly the abuse-related effects of nicotine. In the present study, we characterized the behavioral pharmacological interactions between methylphenidate and nicotine in the intravenous self-administration, drug discrimination, and locomotor cross-sensitization procedures. Adult male Sprague–Dawley rats were trained to respond for intravenous nicotine (0.01 or 0.03 mg/kg/infusion) or sucrose, and the acute effects of methylphenidate (1.25–10 mg/kg) were determined; in addition, separate groups of rats were treated with methylphenidate (2.5 mg/kg) or saline before 12 consecutive nicotine (0.03 mg/kg/infusion) self-administration sessions. Next, the discriminative stimulus effects of nicotine (0.03–0.3 mg/kg) and methylphenidate (1.25–10 mg/kg), alone and in combination with a low nicotine dose (0.056 mg/kg), were tested in nicotine-trained rats. Finally, the locomotor effect of repeated methylphenidate (2.5 mg/kg) was tested in rats previously treated with nicotine (0.2–0.8 mg/kg). Results indicated that acute methylphenidate increased the rate of nicotine self-administration at doses that reduced sucrose-maintained responding; furthermore, tolerance to this effect was not apparent following repeated methylphenidate. Methylphenidate, while not substituting for nicotine alone, dose-dependently enhanced the discriminative stimulus effect of a low nicotine dose. In addition, repeated nicotine exposure promoted the development of locomotor sensitization to methylphenidate. Taken together with recent clinical findings, these results suggest that methylphenidate may enhance the abuse-related behavioral effects of nicotine, perhaps increasing vulnerability to tobacco dependence.