Cocaine abuse has persisted as a major public health concern within the United States for several decades despite substantial efforts to develop therapeutic strategies for its treatment. In particular, medications development efforts have failed to yield a single FDA-approved or generally accepted pharmacotherapy for cocaine dependence. Prominent and problematic consequences of prolonged drug abuse include the persistent devaluation of natural nondrug rewards that previously functioned as effective reinforcers prior to drug exposure, and an increase in the ?incentive salience? of drug-associated stimuli, leading to the model that drugs ?hijack? the brain's natural reward system. The purpose of this proposal is to determine whether a behavioral modification strategy encompassing occasional, unexpected presentation of a high-value, alternate reinforcer will increase the hedonic value and/or motivational salience of a natural reward such that it will reduce cocaine seeking in rats.
In Aim 1, we will use an operant cocaine vs. food choice procedure to determine whether a rare, unexpected reward will shift preferred responding from cocaine to food and alter associated dopamine transmission in the nucleus accumbens.
Aim 2 will examine the consequences of this behavioral manipulation in a model of relapse-like behavior.
Understanding the relationship between natural rewards and drugs of abuse, such as cocaine, is critical for developing medications and behavioral treatment programs that promote abstinence and prevent relapse. The goal of this research project is to use behavioral manipulation of food reward to reduce cocaine seeking in rats. This model could subsequently be used by researchers to identify systems in the brain that could be targeted by medications or behavioral therapy to treat drug addiction.
| Rowson, Sydney A; Foster, Stephanie L; Weinshenker, David et al. (2018) Locomotor sensitization to cocaine in adolescent and adult female Wistar rats. Behav Brain Res 349:158-162 |
| Manvich, Daniel F; Webster, Kevin A; Foster, Stephanie L et al. (2018) The DREADD agonist clozapine N-oxide (CNO) is reverse-metabolized to clozapine and produces clozapine-like interoceptive stimulus effects in rats and mice. Sci Rep 8:3840 |
