Further characterization of varenicline (VAR) and mecamylamine (MEC) and effects on self‐administration (SA) of cocaine (COC) and nicotine (NIC)

Abstract

Studies investigating NIC SA in nonhuman primates is limited despite NIC being one of the most commonly used drugs which is often used in combination with other drugs of abuse. Previous studies in our laboratory found that neither VAR, a nicotinic α4β2 receptor partial agonist, nor NIC functioned as reinforcers when substituted for COC, although both drugs, along with MEC, a nonselective and noncompetitive NIC receptor antagonist, potentiated the discriminative stimulus effects of COC. The present studies further characterize the effects of VAR and MEC in male rhesus monkeys SA NIC (0.001–0.1 mg/kg/injection) on a fixed‐ratio 30 schedule of reinforcement; these animals had a prior history of COC SA. Preliminary results show MEC (0.03–0.3 mg/kg) and VAR (0.1–1.0 mg/kg) functioned as reinforcers when substituted for NIC, suggesting that a history of NIC SA was necessary for MEC and VAR to maintain SA. These results emphasize the importance of evaluating drug history and current drug use when assessing abuse potential of drugs. When given in combination with the dose of NIC that maintained peak response rates, both VAR and MEC attenuated NIC SA. The observation that the behavioral effects of NIC receptor partial agonists and antagonists appear to attenuate NIC‐related behaviors and potentiate COC‐related behaviors supports the hypothesis of a unique role for NIC receptors in stimulant abuse. DA12460