Article

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

ABSTRACT

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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