Journal
BEHAVIOURAL PHARMACOLOGY
Volume 21, Issue 2, Pages 96-103Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FBP.0b013e328336e9c5
Keywords
acetylcholine; addiction; cocaine; dopamine; ethanol; nicotine; reinstatement; relapse; self administration; varenicline
Funding
- NIDA [DA05186, DA026942]
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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. Behavioural Pharmacology 21:96-103 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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