Date Available

4-25-2018

Year of Publication

2018

Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation

College

Arts and Sciences

Department/School/Program

Psychology

First Advisor

Dr. Chana K. Akins

Abstract

A devastating feature of drug-dependence is the susceptibility of relapse (40-60%) after stretches of abstinence. One theory that may account for relapse suggests that drug cues (e.g., paraphernalia) may increase stress hormones, and this may prompt relapse. Repeatedly pairing a neutral cue with a reward is commonly utilized to measure what subjects learn about a cue that is predictive of reward. Research has shown that animals that attend to a cue more than to the reward (sign trackers) may be more vulnerable to drug addiction. Additionally, research has shown that sign tracking is associated with an increase in corticosterone (CORT), a primary stress hormone. PT 150 is a novel glucocorticoid receptor antagonist that attenuates the effects of CORT. Experiment 1 hypothesized that subjects given repeated oral administration of 40 mg/kg PT 150 would reduce sign tracking compared to subjects given placebo. Results of Experiment 1 showed that repeated oral consumption of 40 mg/kg PT 150 decreased sign tracking behavior compared to placebo. In Experiment 2, it was hypothesized that PT 150 (20/40/60 mg/kg) given by subcutaneous (SC) injection would reduce sign tracking dose-dependently, and that sign tracking behavior would correlate with CORT levels. Results of Experiment 2 showed that SC injection of 20 mg/kg PT 150 reduced sign tracking but not 40 or 60 mg/kg. Additionally, the correlation between CORT and the sign tracking for the 20 mg/kg approached significance. Although tentative, the correlation may suggest that elevated plasma CORT concentrations correlate with elevated sign tracking. The current findings extend the current literature by suggesting that the glucocorticoid receptor may be a potential pharmacological target for reducing relapse-like behaviors.

Digital Object Identifier (DOI)

https://doi.org/10.13023/ETD.2018.173

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