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Hathaway, Brett Alexander

University of British Columbia

Deficits in cost/benefit decision making are a critical risk factor for substance use disorder and behavioural addictions such as gambling disorder. Reward-concurrent cues may mediate this relationship, as such stimuli enhance risk preference and can potentiate cocaine intake in rats. To investigate the influence of cues on brain functioning and cost/benefit decision making, we utilize the rat Gambling Task. This task was designed such that maximal reward is attained by avoiding the high-risk, high-reward options and instead favouring the options associated with lower per-trial gains, as they feature less frequent and shorter time-out penalties. Adding reward-paired audiovisual cues to the task leads to greater risky choice on average. As inflexible pursuit of rewards is a critical component of drug and behavioural addictions, I tested whether these cues can also induce inflexibility in choice patterns. Results showed that win-paired cues but not loss-paired or randomly occurring cues drive risky choice as well as inflexibility in responding following shifts in reinforcer value. I also investigated potential neurobiological mechanisms of the impact of cues on decision making. I showed that altering serotonergic signaling in the lateral OFC can both ameliorate cue-induced risky choice and restore sensitivity to reinforcer devaluation. Furthermore, I showed that altering lateral OFC activity differentially affects choice patterns during early task learning on the uncued versus cued rGT, further demonstrating that OFC output is substantially impacted by the inclusion of cues on the task. I also showed that dopamine activity in the dorsal striatum is involved in the development and performance of choice patterns on the cued rGT, at least in females; inhibiting dopamine pathways projecting to the dorsal striatum resulted in an initial increase in risky choice followed by a subsequent long-term improvement in decision making. Thus, the role of dopamine in guiding choice towards versus away from risky options on the cued rGT shifts over time. Overall, these results shed light on the interaction between reward-paired cues, risky choice, and inflexible responding, thus providing insight into cue-induced compulsive risky behaviours that underlie both substance use disorder and gambling disorder.

Text

2023-04-20

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/84359

Neuroscience

University of British Columbia

UBCV

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