Activation of the dynorphin-kappa opioid receptor (KOR) system produces a negative emotional state during drug withdrawal, thereby motivating continued cocaine-seeking behaviors. However, it is not clear whether dynorphin plays a functional role in the onset of compulsive cocaine-taking. Here, escalation of cocaine self-administration was significantly attenuated by pretreatment of a long-acting KOR antagonist, norbinaltorphimine (NBI), in long access (LgA; 6-hours) male rats, whereas there was no effect of NBI on short access (ShA; 1-hour) rats on a fixed or progressive ratio schedule of reinforcement. Additionally, optical density of prodynorphin was increased in the nucleus accumbens (NAc) core and shell, bed nucleus of the stria terminalis (BNST), central amygdala (CeA), and basolateral amygdala (BLA) of LgA rats compared to both ShA and drug-naïve rats. These results suggest dynorphin in the stress-sensitive extended amygdala (NAc shell, BNST, CeA), and BLA-NAc core circuitry mediating cue-controlled cocaine-taking may be associated with the onset of compulsive drug-taking.
| Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etd-5969 |
| Date | 01 August 2024 |
| Creators | Lord, Jessica |
| Publisher | Digital Commons @ East Tennessee State University |
| Source Sets | East Tennessee State University |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Electronic Theses and Dissertations |
| Rights | Copyright by the authors. |
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