Effects of chronic varenicline treatment on nicotine, cocaine, and concurrent nicotined plus cocaine self-administration

Abstract

Nicotine dependence and cocaine abuse are major public health problems, and most cocaine abusers also smoke cigarettes. An ideal treatment medication would reduce both cigarette smoking and cocaine abuse. Varenicline is a clinically available, partial agonist at alpha 4 beta 2* and alpha 6 beta 2* nicotinic acetylcholine receptors (nAChRs) and a full agonist at alpha 7 nAChRs. Varenicline facilitates smoking cessation in clinical studies and reduced nicotine self-administration, and substituted for the nicotine-discriminative stimulus in preclinical studies. The present study examined the effects of chronic varenicline treatment on self-administration of IV nicotine, IV cocaine, IV nicotine + cocaine combinations, and concurrent food-maintained responding by five cocaine- and nicotine-experienced adult rhesus monkeys (Macaca mulatto). Varenicline (0.009-0.04 mg/kg/h) was administered intravenously every 20 min for 23 h each day for 7-10 consecutive days. Each varenicline treatment was followed by saline-control treatment until food- and drug-maintained responding retumed to baseline. During control treatment, nicotine + cocaine combinations maintained significantly higher levels of drug self-administration than nicotine or cocaine alone (P