Thesis
Cue-induced impulsive-like behavior: role of Kappa-opioid receptor activation
Washington State University
Master of Science (MS), Washington State University
05/2015
Handle:
https://hdl.handle.net/2376/101257
Abstract
Impulsivity is a major component of alcohol and drug abuse disorders yet little research has examined the role of the kappa-opioid receptor (KOR) / dynorphin (DYN) system in this type of maladaptive behavior. It has been observed that DYN A peptide expression and KOR signaling are upregulated in the amygdala of alcohol-dependent rodents and that central KOR activation leads to increased impulsive-like responding on the stop-signal reaction time (SSRT) but not delay discounting (DD) task. Furthermore, blockade of KORs attenuates escalated alcohol self-administration in dependent rats and reduces impulsive behaviors on the SSRT task. Cues initially paired with KOR activation escalate alcohol self-administration in non-dependent rats and create negative affective-like states mimicking those observed during alcohol withdrawal. Given that cues associated with drug withdrawal increase drug seeking and subsequent relapse (i.e., impulsive-like behaviors) and that direct KOR activation produces dissociable effects on the SSRT and DD tasks, it is hypothesized that presentation of an olfactory cue initially paired with central KOR activation will increase impulsive-like responding on the SSRT but not DD task. To test this hypothesis, separate cohorts of male Wistar rats were trained on the SSRT or DD task until stable responding was established. Next, SSRT rats were trained on a series of stop-signal delays (SSDs), which were calculated by taking the mean reaction time (mRT) and subtracting predetermined intervals from this value. DD rats were tested on sessions containing six delay intervals of increasing magnitude for the large reinforcer. All rats were classically conditioned to an olfactory stimulus with infusions of KOR agonist U50,488 or vehicle. On the final test day, rats were presented with the cue alone prior to operant testing. The results revealed a trend towards significantly increased impulsive-like behavior following exposure to a cue initially paired with KOR activation for the SSD mRT-300 ms cohort. These findings implicate a potential neurobiological dissociation of KOR activation between SSRT and DD measures. A deeper understanding of cue-induced impulsivity and the role of the KOR / DYN system will ultimately lead to improved pharmacological treatments for a host of neuropsychiatric disorders including alcohol and substance abuse disorders.
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Details
- Title
- Cue-induced impulsive-like behavior
- Creators
- Jessica Lynne Kissler
- Contributors
- Brendan M. Walker (Chair)Rebecca M. Craft (Committee Member)John M Hinson (Committee Member) - Washington State University, Psychology, Department of
- Awarding Institution
- Washington State University
- Academic Unit
- Psychology, Department of
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University; [Pullman, Washington] :
- Number of pages
- 47
- Identifiers
- 99900525151301842
- Language
- English
- Resource Type
- Thesis