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Russell, Brittney

University of British Columbia

Cue reactivity is well-recognized in addiction and predicts symptom severity and treatment outcomes. Pavlovian learning and incentive sensitization are potential mechanisms enabling cues to capture attention, induce craving, and promote risk. Animal research implies trait-like variation in the degree of incentive salience attributed to reward-associated cues, defined phenotypically as sign-trackers (STs; high) and goal-trackers (GTs; low incentive salience), that has been linked to addiction features. Chapter 2 examines whether ST/GT phenotype and problematic gambling involvement modulate the effect of reward-associated cues on decision making. Sign-tracking was measured in a Pavlovian conditioning task as the amount of eye gaze fixation on the reward-predictive cue versus the location of impending reward delivery. STs made riskier value-dependent choices than GTs, but this had contrasting effects depending on gambling involvement. Among the control group, STs were riskier than GTs; however, GTs were riskier than STs in the problem gambling group. These effects were not dependent on cues, suggesting that incentive salience is not increasing risk. On a rat model of decision making (cued rat Gambling task), cues have been consistently shown to promote risk. The effect of cues can be amplified with chronic administration of the dopamine D2/3 receptor agonist ropinirole during task acquisition. Chapter 3 examines sex differences in cue-driven decisional risk and the specific receptors underlying ropinirole’s effects. Ropinirole increased decisional risk and impulsivity, but there were no sex differences in decisional risk, opposing previous findings of sexually dimorphic effects of dopamine modulation on this task. Chronic selective agonism of either the D2 or D3 receptor with doses that target only the autoreceptor or additional postsynaptic receptors did not mirror ropinirole’s effects. Unlike ropinirole, combined administration of D2 and D3 selective agonists improved decision making. Together, these findings suggest that ropinirole has a psychostimulant-like effect on behaviour, unlike any other dopamine agonist. Ropinirole’s mechanism to evoke risk is not solely through the D2 and D3 receptors, as individual or combined activation of these receptors typically had advantageous effects on decision making and impulsivity. Understanding ropinirole’s mechanism and the stability of trait-like addiction vulnerability would provide further insight into the progression of addiction.

Text

2024-09-03

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/89147

Psychology

University of British Columbia

UBCV

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