Acquisition of nicotine discrimination and discriminative stimulus effects of nicotine in rats chronically exposed to caffeine

Maciej Gasior, Mohammed Shoaib, Sevil Yasar, Maria Jaszyna, Steven R. Goldberg

Research output: Contribution to journalArticle

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 (022%). There was no generalization to the nicotine cues after i.p. treatment with caffeine or the selective D2 (NPA) and D3 (PO 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.

Original languageEnglish (US)
Pages (from-to)1053-1073
Number of pages21
JournalJournal of Pharmacology and Experimental Therapeutics
Volume288
Issue number3
StatePublished - Mar 1999

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Caffeine
Nicotine
Drinking Water
Cues
Drinking
Discrimination (Psychology)
Dopamine Agonists
Cocaine
Dopamine Uptake Inhibitors
Nicotinic Antagonists
Mecamylamine
Dopamine D1 Receptors
Dopamine Agents
Dextroamphetamine
Water
Apomorphine
Coffee
Nicotinic Receptors
Street Drugs
Amphetamine

ASJC Scopus subject areas

  • Pharmacology

Cite this

Acquisition of nicotine discrimination and discriminative stimulus effects of nicotine in rats chronically exposed to caffeine. / Gasior, Maciej; Shoaib, Mohammed; Yasar, Sevil; Jaszyna, Maria; Goldberg, Steven R.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 288, No. 3, 03.1999, p. 1053-1073.

Research output: Contribution to journalArticle

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