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Effects of varenicline on the reinforcing and discriminative stimulus effects of cocaine in rhesus monkeys
Author(s) -
Gould Robert Warren,
Czoty Paul W,
Nader Susan H,
Nader Michael A
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.588.6
Subject(s) - varenicline , pharmacology , nicotine , agonist , stimulus control , partial agonist , self administration , psychology , medicine , neuroscience , receptor
In the CNS, stimulation of nicotinic acetylcholine receptors (nAChR) can directly affect dopaminergic tone and may, therefore, modulate the reinforcing effects of abused drugs. In rhesus monkeys, we examined the nAChR partial agonist varenicline and full agonist nicotine in i.v. drug self‐administration and cocaine discrimination procedures. When substituted for cocaine in monkeys responding under a progressive‐ratio (PR) schedule, nicotine (0.03‐0.3 mg/kg) but not varenicline (0.01‐0.17 mg/kg) functioned as a reinforcer. When administered chronically, varenicline (titrated up to 0.3 mg/kg, BID p.o. by day 30) did not affect cocaine break point under the PR schedule or cocaine intake. In monkeys discriminating 0.3 mg/kg i.v. cocaine from saline, varenicline (0.03‐0.3 mg/kg, i.v.) did not engender cocaine‐like discriminative stimulus effects, but dose‐dependently potentiated the effects of cocaine when administered 60 min prior to testing. These preliminary results indicate low abuse liability for the nAChR partial agonist varenicline but suggest that varenicline may potentiate the subjective effects of cocaine. Future studies will investigate nAChR compounds of varying intrinsic efficacy and subtype specificity to further understand the role of nAChRs in mediating the reinforcing and discriminative stimulus effects of cocaine. All doses are expressed as that of the salt. DA12460.