Author ORCID Identifier

https://orcid.org/0000-0001-5999-145X

Date Available

12-6-2018

Year of Publication

2018

Document Type

Doctoral Dissertation

Degree Name

Doctor of Philosophy (PhD)

College

Arts and Sciences

Department/School/Program

Psychology

Advisor

Dr. Joshua S. Beckmann

Abstract

Cocaine use disorder is a significant health problem, negatively impacting individuals afflicted. While preclinical self-administration research has provided invaluable insight into the neurobehavioral mechanisms that underlie cocaine abuse, cocaine use outside of the laboratory occurs within an environment where other goods are also available ubiquitously. Although there is an ever-increasing literature investigating drug vs. non-drug choice in rodent models and how alternative goods can compete with the subjective value of cocaine, the neurobiological mechanisms that are associated with cocaine preference remains largely unknown. Additionally, current drug vs. non-drug choice studies use procedures that confound preference with intake, such that preference measures are directly reflective of individual experience with drug and non-drug reinforcers earned through the choices that are made; simply, preference and intake are the same. Moreover, differences in cocaine experience can result in differential neural adaptations, thus making it difficult to determine if the neurobiological mechanisms underlying choice are related to preference or drug intake. Herein a novel choice procedure, which controls for reinforcer intake (controlled reinforcer ratio; CRR), was used to explore how certain reinforcer dimensions (i.e., magnitude and frequency) influence cocaine preference. In addition, neuronal activity, measured via c-fos expression, in the orbitofrontal cortex and nucleus accumbens, areas associated with decision-making and valuation, for cocaine and food were independently targeted and labeled using fluorescent in situ hybridization and fluorescent immunohistochemistry. First, unlike prototypical choice procedures where preference and intake are confounded, the CRR choice procedure was able to dissociate the two. Under the CRR choice procedure, it was revealed that both magnitude and frequency, independent dimensions of reinforcement, greatly influence preference for cocaine. Furthermore, the CRR choice procedure was sensitive to manipulations known to influence cocaine preference while keeping reinforcer intake constant. When neuronal activity was examined after CRR training, the number of cocaine activated cells, relative to food activated cells, did not correlate with individual preferences for cocaine despite overall reinforcer intake being held constant. Instead, results suggest neuronal activity for cocaine was related to overall cocaine intake. Overall, these results give impetus for utilizing the CRR choice procedure to better investigate how drug and non-drug reinforcers are afforded differential subjective value and compete for preference. Moreover, use of a CRR choice procedure may lead to identification of specific neurobehavioral mechanisms and lead toward future development of more effective pharmacological and behavioral treatments to ameliorate substance use disorders.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2018.497

Funding Information

DA033373

DA045023

DA016176

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