Subjective and objective evidence of low abuse potential of the peripherally-acting kappa opioid, CR845, compared with pentazocine

Drug and Alcohol Dependence 156 (2015) e183–e245 e211 preclinical model used to develop and test potential pharmacotherapies is the rodent intravenous (i.v.) self-administration paradigm. The aim of the current study was establish rodent i.v. self-administration under a multiple schedule with alternating components ofMETHand food reinforcement. Once behavior stabilized on this schedule we tested two potential pharmacotherapies for METH addiction: GZ-793A, a vesicular monoamine transporter 2 (VMAT2) inhibitor and varenicline, a partial agonist at a4b2 nicotinic acetylcholine receptors (nAChR). Methods: Following catheterization surgery, male SpragueDawley rats acquired both i.v. METH (0.3mg/kg/infusion) and food self-administration under a multiple schedule of reinforcement. Following stable responding pretreatments of GZ-793A (0, 10, 15, or 30mg/kg, s.c.) and varenicline (0, 0.3, 1, or 2mg/kg, s.c.) were administered in a Latin Square design with half of the animals receiving GZ-793A first while the other half received varenicline first. Results: Both GZ-793A and varenicline decreased METH self-administration. However, GZ-793A was more selective at decreasing METH intake without altering food-maintained responding. More specifically, the 20mg/kg of GZ-793A significantly decreased METH intake compared to saline without effecting food-maintained responding. Also, the lowest dose of GZ-793A significantly decreased METH intake compared to the lowest dose of varenicline, againwithout disrupting food-maintained responding. Nodoseofvarenicline significantly loweredMETH intakecompared to a saline control. Conclusions: Cumulatively, this suggests that VMAT2 inhibition, rather than nAChR partial agonism, is a more promising avenue to pursue for a potential pharmacotherapy forMETH addiction. Financial Support: This project was funded by the Ferlic Summer Research Fund to MMK. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.568 Women’s intervention to stop HIV/HCV (WISH) Michele Staton-Tindall 5,∗, Matthew Webster3, Carl Leukefeld2, Jennifer R. Havens4, Carrie B. Oser1 1 Sociology, University of Kentucky, Lexington, KY, United States 2 University of Kentucky, Lexington, LA, United States 3 Behavioral Science, University of Kentucky, Lexington, KY, United States 4 Center on Drug and Alcohol Research, University of Kentucky, Lexington, KY, United States 5 Social Work, University of Kentucky, Lexington, KY,