Undergraduate Honors Theses

Thesis Defended

Spring 2013

Document Type

Thesis

Department

Psychology & Neuroscience

First Advisor

Dr. Ryan Bachtell

Abstract

Cocaine addiction is a brain disorder that negatively affects the lives of millions of people and causes great societal harm. Most people who try cocaine do not become addicted to it. What predisposes someone to develop a cocaine dependency while others are able to control use is not well understood. This study’s aim is to use a novel rat model of dopamine D2 autoreceptor sensitivity to assess addiction vulnerability. We have found that rats with a high D2 autoreceptor sensitivity (PreHD2) are more sensitive to both the rewarding and psychomotor stimulating effects of cocaine than rats with a low D2 autoreceptor sensitivity. We have found several neurobiological alterations within the nigrostriatal pathway, a region intimately involved in the motor behaviors of drugs of abuse that correlate with this differential behavioral profile. We found that PreHD2 rats had decreased expression of adenosine A2A receptor, D2 receptor, Dopamine Transporter, and DARPP-32 within the Caudate Putamen, and decreased expression of Dopamine Transporter and Tyrosine Hydroxylase within the Substantia Nigra. We also found differential activity-dependent phosphorylation of several phosphoproteins (pTHSer40 and pDARPP-32Thr34) between PreHD2 and PreLD2 animals within the nigrostriatal pathway.

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