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Hrelja, Kelly M.

University of British Columbia

Impaired decision-making is recognized as a diagnostic criterion for many different psychiatric disorders including gambling disorder and substance use disorders. Habit formation and cue responsivity are known to play a role in driving these disorders, but less is known as to if and how decision-making is differentially altered by different classes of abused drugs. The impact of biological sex is also vastly understudied in such contexts. To gain further understanding on the bi-directional relationship between decision-making impairments and addiction, we combined the well-established rat gambling task with volitional drug self-administration in both male and female rats. In one aim, I sought to pharmacologically manipulate habit formation via the systemic administration of a histone deacetylation inhibitor. I found that inhibiting histone deacetylation resulted in increased risky choice during acquisition of our rat gambling task, while also altering how rats were learning from task outcomes. In another aim, I sought to further characterize the effect of cues on decision-making by allowing rats to choose between the cued and uncued rat gambling task on a trial-by-trial basis. I found that cues had negative effects on cognition, despite being preferred to their absence. I then paired this task with cocaine self-administration to investigate the bi-directional effects of gambling and cocaine-taking. I found evidence for cocaine-induced motivational deficits on subsequent gambling sessions. In my final aim, I sought to determine whether fentanyl could induce the same decision-making impairments that we had previously observed in response to cocaine. I found that while acute fentanyl self-administration did not impact cognition, fentanyl withdrawal did have long-lasting negative effects on decision-making.

Text

2024-04-10

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/87754

Neuroscience

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/