Drug and Alcohol Dependence 85 (2006) 213–220 Influence of abstinence and conditions of cocaine access on the reinforcing strength of cocaine in nonhuman primates Paul W. Czoty a , Jennifer L. Martelle a , Michael A. Nader a,b,∗ a Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1083, United States b Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, United States Received 28 February 2006; received in revised form 13 April 2006; accepted 18 April 2006 Abstract The development of addiction is marked by a transition from recreational to uncontrolled drug use. Investigators modeling this phenomenon in rodents observed increases in cocaine self-administration when conditions of drug access were altered as well as after abstinence. The present studies were designed to extend this research to nonhuman primates by examining whether the reinforcing strength of cocaine could be altered by changing conditions of cocaine availability or by introducing abstinence periods. Rhesus monkeys self-administered cocaine (0.03–0.3 mg/kg per injection) under a progressive-ratio (PR) schedule of reinforcement in evening sessions, with the number of injections earned serving as a measure of reinforcing strength. Alterations in the reinforcing strength of cocaine were assessed after additional access to cocaine under a fixed-ratio (FR) schedule was provided in morning sessions and following various periods of abstinence (3, 7 and 14 days) from regimens of self-administration that resulted in a range of cocaine intakes. Under baseline PR conditions, the maximum number of cocaine injections increased dose-dependently, peaking when 0.3 mg/kg per injection cocaine was available. No increases in the reinforcing strength of cocaine were observed under any condition. In contrast, a statistically significant decrease in the reinforcing strength of cocaine was observed following 14 days of abstinence under one condition. These results fail to support the views that increasing access to cocaine or abstinence enhances the reinforcing strength of cocaine. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Model of addiction; Reinforcing efficacy; Self-administration; Progressive-ratio; Rhesus monkey 1. Introduction Intravenous drug self-administration techniques have demon- strated predictive validity in characterizing the abuse liability of centrally acting drugs (Griffiths et al., 1980; Ator and Griffiths, 2003) and have been used extensively to evaluate candidate pharmacotherapies for cocaine abuse (Mello and Negus, 1996; Carroll et al., 1999; Platt et al., 2002). Procedures typically used to examine self-administration involve limited daily access to cocaine, which results in stable rates of responding and patterns of cocaine intake. Such stable behavioral baselines have helped to elucidate the neurobiological mechanisms that mediate the ∗ Corresponding author at: Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1083, United States. Tel.: +1 336 713 7172; fax: +1 336 713 7168. E-mail address: mnader@wfubmc.edu (M.A. Nader). reinforcing effects of cocaine (e.g., Ritz et al., 1987; Bergman et al., 1990). However, such procedures fail to address the pro- gression from recreational to uncontrolled use that marks the development of addiction (Gawin and Ellinwood, 1988; Gawin, 1991; Dackis and O’Brien, 2001). One approach to modeling uncontrolled drug use is to provide laboratory animals with unlimited access to cocaine. However, early studies demonstrated that unlimited access resulted in cocaine intakes sufficiently high to produce severe toxicity in rats and monkeys and death within as little as 5 days of expo- sure in monkeys (Deneau et al., 1969; Johanson et al., 1976; Aigner and Balster, 1978; Bozarth and Wise, 1985). Although the majority of subsequent studies have avoided toxicity by con- straining cocaine availability, more recent studies in rodents have attempted to model “loss of control” over cocaine self- administration using conditions under which rats have extended access to cocaine under fixed-ratio (FR) schedules in the absence of toxic and/or lethal effects (e.g., Fitch and Roberts, 1993; 0376-8716/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.drugalcdep.2006.04.009