The purpose of this project is to examine the effects of alternative nondrug reinforcement on stimulant self-administration in rats. The long-term goal is to develop a model of reinforcement-based clinical interventions for stimulant abuse that can be used to examine techniques to increase the efficacy of such interventions and provide a clinically relevant platform for preclinical medications development. In animal models of drug abuse, the prominence of research on neuropharmacological mechanisms that mediate the reinforcing effects of stimulants has resulted in much less emphasis on the important role that environmental variables play in stimulant drug self-administration, as well as their role in modulating the efficacy of medications in reducing drug self-administration. Given the superior clinical efficacy of combining behavioral and pharmacological treatments, this relative lack of emphasis on environmental variables may limit the contributions of animal research to the development of more effective combined treatments for stimulant abuse. One of the most effective behavioral treatments for stimulant abuse is contingency management (CM), which involves delivery of alternative reinforcers contingent upon abstinence from drug use. In preliminary studies, novel preclinical models of CM interventions for drug abuse have been developed and shown to significantly reduce drug self-administration in rats. The primary model employs a differential-reinforcement-of-alternative-behavior (DRA) schedule of alternative nondrug reinforcement, in which availability of an alternative reinforcer (e.g., sucrose pellets) is made contingent upon abstinence from drug self-administration.
Specific Aim #1 is to characterize this model further by examining the generality of the effects a DRA schedule of alternative nondrug reinforcement across different unit doses and types of stimulant (nicotine and cocaine) maintaining responding.
Specific Aim #2 is to examine whether the extent of reduction produced by a DRA schedule is enhanced by environmental variables, such as magnitude of alternative reinforcement and presentation of stimuli paired with alternative reinforcement.
Specific Aim #3 is to examine whether the extent of reduction is increased by combining the DRA schedule with pharmacological treatment. These studies should provide a useful preclinical model of CM interventions and be helpful in elucidating behavioral and pharmacological variables that could enhance their efficacy. ? ?
| Sofuoglu, Mehmet; LeSage, Mark G (2012) The reinforcement threshold for nicotine as a target for tobacco control. Drug Alcohol Depend 125:1-7 |
| LeSage, Mark G; Perry, Jennifer L; Kotz, Catherine M et al. (2010) Nicotine self-administration in the rat: effects of hypocretin antagonists and changes in hypocretin mRNA. Psychopharmacology (Berl) 209:203-12 |
| LeSage, Mark G; Shelley, David; Ross, Jason T et al. (2009) Effects of the nicotinic receptor partial agonists varenicline and cytisine on the discriminative stimulus effects of nicotine in rats. Pharmacol Biochem Behav 91:461-7 |
| Lesage, Mark G (2009) Toward a nonhuman model of contingency management: effects of reinforcing abstinence from nicotine self-administration in rats with an alternative nondrug reinforcer. Psychopharmacology (Berl) 203:13-22 |
| Lerman, Caryn; Lesage, Mark G; Perkins, Kenneth A et al. (2007) Translational research in medication development for nicotine dependence. Nat Rev Drug Discov 6:746-62 |
