Effects of Restraint Stress and Allopregnanolone Inhibition on Amphetamine Locomotor Sensitivity

The chronic, recurring nature of addiction remains a worldwide problem. Even after apparently successful clinical treatment and long term abstinence, individuals may still relapse many months or years later. Although many individual differences exist among substance abusers, relapse tends to occur during periods of high stress (Sinha et al., 2006). Behavioral training and therapy can help cope during these high stress times, but pharmacological interventions have not been shown to be effective (Ross & Peselow, 2009). Although some therapeutic options decrease relapse rates, more effective treatments for relapse need further consideration. The effect of stress on use of and relapse to drugs of abuse likely stems from coupled stress and reward circuits in the brain. Stress leads to increased release of stress-related hormones including 3α, 5α tetrahydroprogesterone or, allopregnanolone (Purdy et al., 1991). Allopregnanolone is a neurosteroid tied to several brain circuits involved with stress and reward. Elevated levels of this neurosteroid occur throughout the mammalian brain and periphery after cocaine administration, and rats show enhanced dopamine release in the nucleus accumbens after an injection of finasteride, which inhibits the enzymes (5-α reductase I) responsible for allopregnanolone synthesis (Dazzi et al., 2002). Finally, acutely stressed rats exhibit increased dopamine release in the prefrontal cortex after an injection of finasteride, further indicating allopregnanolone’s involvement with brain reward systems (Devoto, 2012). Based on this information, we hypothesized that administration of finasteride would result in increased stress induced amphetamine locomotor sensitization

McNair Research Journal - Summer 2015

Journal articles based on research conducted by undergraduate students in the McNair Scholars Program Table of Contents Biography of Dr. Ronald E. McNair Statements: Dr. Neal J. Smatresk, UNLV President Dr. Juanita P. Fain, Vice President of Student Affairs Dr. William W. Sullivan, Associate Vice President for Retention and Outreach Mr. Keith Rogers, Deputy Executive Director of the Center for Academic Enrichment and Outreach McNair Scholars Institute Staf