Date of Award
Doctor of Philosophy (PhD)
People with neuropathologies who are treated with dopamine agonists may be at risk to develop impulse control disorders. The overall goal of this dissertation project was to expand our knowledge on the neuropsychopharmacology of dopamine agonist-induced impulsivity. At the time this dissertation was being developed, pramipexole was the drug, gambling was the behavior, and Parkinson's disease (PD) was the pathology most widely reported for this phenomenon. Therefore, we first developed a behavioral paradigm (i.e., probability discounting) to measure risk-taking, one aspect of gambling. Utilizing this paradigm, we determine if risk-taking was altered after acute and/or chronic pramipexole treatment. We incorporated an animal model of PD in this study to determine if a PD-like brain state alters the response of pramipexole in the discounting paradigm. The final series of studies focused on determining if a limbic brain region involved in reward-related behaviors is also altered by acute and/or chronic pramipexole exposure. Work from our laboratory and others suggest that the ventral pallidum (VP) would be a region of interest. The VP mediates responses to rewards and VP neural activity integrates predictive, incentive, and reward value information. As studies show that pramipexole can alter aspects of impulsivity, such as risk-taking, and enhance motivational salience of reward-related cues, it is possible that the VP plays a role in mediating effects of pramipexole. Accordingly, we hypothesized that VP neuronal activity is altered by behaviorally relevant doses of pramipexole. We utilized single-cell extracellular electrophysiological techniques to investigate effects of systemic pramipexole on VP neuronal firing rate. Finally, as D3Rs can mediate reward-seeking behavior, we investigated the influence of D3Rs in the ability of pramipexole to alter VP neuronal firing rate using PG01037, a D3R-preferring antagonist. Collectively, my studies demonstrate that acutely administered pramipexole enhances risk-taking in rats and also modulates VP neuronal firing rate; this modulation appears to be mediated by D3R activation. Chronic pramipexole treatment enhances risking-taking compared to acute treatment. Chronic treatment also enhances the potency of PPX to alter VP neuronal firing rate. Finally, these studies suggest that a PD-like brain state does not alter pramipexole-induced alterations in risk-taking.
Rokosik-Kletzel, Sandra Lynn, "Influence of Pramipexole on Probability Discounting and Ventral Pallidal Function: Assessments in Parkinsonian-Like Rats" (2013). Dissertations. 732.
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Copyright © 2013 Sandra Lynn Rokosik-Kletzel