Abstract
Caffeine and nicotine are the main psychoactive ingredients of coffee and tobacco, with a high frequency of concurrent use in humans. This study examined the effects of chronic caffeine exposure on 1) rates of acquisition of a nicotine discrimination (0.1 or 0.4 mg/kg, s.c., training doses) and 2) the pharmacological characteristics of the established nicotine discrimination in male Sprague-Dawley rats. Once rats learned to lever-press reliably under a fixed ratio of 10 schedule for food pellets, they were randomly divided into two groups; 12 animals were maintained continuously on caffeine added to the drinking water (3 mg/ml) and another 12 control rats continued to drink tap water. In each group of water- and caffeine-drinking rats, there were six rats trained to discriminate 0.1 mg/kg of nicotine from saline and six rats trained to discriminate 0.4 mg/kg of nicotine from saline. Regardless of the training dose of nicotine, both water- and caffeine-drinking groups required a comparable number of training sessions to attain reliable stimulus control, although there was a trend for a slower acquisition in the caffeine-drinking group trained with 0.1 mg/kg of nicotine. Tests for generalization to different doses of nicotine revealed no significant differences in potency of nicotine between water- and caffeine-drinking groups. The nicotinic-receptor antagonist mecamylamine blocked the discriminative effects of 0.1 and 0.4 mg/kg nicotine with comparable potency and efficacy in water- and caffeine-drinking groups. There was a dose-related generalization to both the 0.1 and 0.4 mg/kg nicotine cue (maximum average of 51–83%) in water-drinking rats after i.p. treatment with d-amphetamine, cocaine, the selective dopamine uptake inhibitor GBR-12909, apomorphine, and the selective dopamine D1 receptor agonist SKF-82958, but not in caffeine-drinking rats (0–22%). There was no generalization to the nicotine cues after i.p. treatment with caffeine or the selective D2 (NPA) and D3 (PD 128,907) dopamine-receptor agonists in water- and caffeine-drinking rats. The dopamine-release inhibitor CGS 10746B reduced the discriminative effects of 0.4 mg/kg nicotine in water-drinking rats, but not in caffeine-drinking rats. There was no evidence of development of tolerance or sensitization to nicotine’s effects throughout the study. In conclusion, chronic caffeine exposure (average, 135 mg/kg/day) did not affect the rate of acquisition of the nicotine discrimination, but it did reduce the dopaminergic component of the nicotine-discriminative cue. The reduction of the dopaminergic component of the nicotine cue was permanent, as this effect was still evident after the caffeine solution was replaced with water in caffeine-drinking rats. That nicotine could reliably serve as a discriminative stimulus in the absence of the dopaminergic component of its discriminative cue may differentiate nicotine from “classical dopaminergic” drugs of abuse such as cocaine and amphetamine.
Footnotes
-
Send reprint requests to: Maciej Gasior, M.D., Ph.D., Preclinical Pharmacology Laboratory, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, 5500 Nathan Shock Drive, Baltimore, MD 21224. E-mail: mgasior{at}intra.nida.nih.gov
-
↵3 A Visiting Fellow in the National Institutes of Health Visiting Program of the Fogarty International Center, Bethesda, MD. Permanent address: Department of Pharmacology, Medical University School, Lublin, Poland.
-
↵4 Present address: Institute of Psychiatry, De Crespigny Park, Denmark Hill, London, United Kingdom.
-
↵5 Present address: Division of Gerontology and Geriatric Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224.
-
↵1 This work was supported by National Institute on Drug Abuse/National Institutes of Health, Baltimore MD.
-
↵2 Animals used in these studies were maintained in facilities fully accredited by the American Association for the Accreditation of Laboratory Animal Care and all experimentation was conducted in accordance with the guidelines of the Institutional Care and Use Committee of the National Institute on Drug Abuse, National Institutes of Health, and the Guide for Care and Use of Laboratory Animals (National Research Council, 1996, National Academy Press, Washington, DC). Preliminary findings of this study were presented at the Annual Meeting of the International Behavioral Neuroscience Society, San Diego, CA, April 24–27, 1997 [Gasior M, Shoaib M, Yasar S and Goldberg SR (1997) Qualitative changes in the discriminative properties of nicotine produced by chronic caffeine exposure in rats. Abstract of the International Behavioral Neuroscience Society 6:54] and during the XIIIth Congress of the Polish Pharmacological Society, Katowice, Poland, September 13–16, 1998 [Gasior M and Goldberg SR (1998) Influence of chronic caffeine exposure on the behavioral effects of nicotine: Implications for abuse potential. Pol J Pharmacol50 (Suppl):61].
- Abbreviations:
- ACh
- acetylcholine
- FI
- fixed interval
- FR
- fixed ratio
- Received July 14, 1998.
- Accepted October 8, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|