Varenicline effects on cocaine self administration and reinstatement behavior

Department of Integrative Neurophysiology, CNCR, VU University, Amsterdam, The Netherlands.
Behavioural pharmacology (Impact Factor: 2.15). 03/2010; 21(2):96-103. DOI: 10.1097/FBP.0b013e328336e9c5
Source: PubMed


This study tested the effects of the nicotine addiction treatment varenicline on cocaine self administration (SA) and reinstatement. In one SA experiment, rats were trained to self-administer cocaine (0.75 mg/kg/infusion). Thereafter, daily SA sessions continued as before except that every fourth session was preceded by a presession injection of varenicline (0.0, 0.3, 1.0 and 2.0 mg/kg, SC, 50-min presession). In three reinstatement experiments, animals were exposed sequentially to SA training, extinction training, and several reinstatement test sessions. In two of the reinstatement experiments, cocaine-seeking was reinstated by presentation of cocaine-predictive cues at the onset of the test session (cue reinstatement). In a third reinstatement experiment, cocaine-seeking was reinstated by a presession injection of cocaine (drug reinstatement). Each reinstatement session was preceded by an injection of either vehicle or varenicline (dose range of 0.1-2.0 mg/kg). The SA and reinstatement experiments showed that low-dose varenicline decreases reinstatement behavior, without significantly affecting cocaine SA. In contrast, high-dose varenicline increases reinstatement of cocaine-directed behavior and decreases cocaine SA. A control study showed that sucrose-directed behavior is unaltered by varenicline. On the basis of these findings, low-varenicline doses might decrease relapse in cocaine-addicted individuals, but high doses of varenicline might have the opposite effect.

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    • "With regard to other psychostimulants, a number of nACR antagonists were found to decrease cocaine self-administration, prevent cue-induced craving for cocaine, and to decrease cocaine effects in a place preference paradigm or reduce cocaine-induced behavioral sensitization (Levin et al., 2000; Zachariou et al., 2001; Champtiaux et al., 2006; Hansen and Mark, 2007) suggesting a direct involvement of nAChRs in cocaine-taking and -seeking behavior. In addition, recent studies indicate that varenicline reduces cocaine-induced reward in rodents and humans (Guillem and Peoples, 2010; Plebani et al., 2012). In contrast, varenicline was found ineffective in reducing cocaine self-administration in a primate model (Gould et al., 2011), indicating mixed effects across models which may be due to species' differences . "
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    • "In measures of abuse liability, varenicline has been shown to substitute for nicotine in drug discrimination and functioned as a reinforcer when substituted for nicotine on a progressive-ratio (PR) schedule in rats (Rollema et al., 2007). In a reinstatement model in rats previously trained to self-administer cocaine, a high dose of varenicline increased cue-induced reinstatement (Guillem and Peoples, 2010). However, Desai and Bergman (2010) recently found that although nicotine completely substituted for the methamphetamine stimulus, varenicline did not substitute and did not attenuate the discriminative stimulus effects of the training dose of methamphetamine. "
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