Irrational Choice under Uncertainty Correlates with Lower Striatal D_2/3Receptor Binding in Rats

Abstract

Individual differences in dopamine (DA) signaling, including low striatal D 2/3 receptors, may increase vulnerability to substance abuse, although whether this phenotype confers susceptibility to nonchemical addictions is unclear. The degree to which people use "irrational" cognitive heuristics when choosing under uncertainty can determine whether they find gambling addictive. Given that dopaminergic projections to the striatum signal reward expectancy and modulate decision-making, individual differences in DA signaling could influence the extent of such biases. To test this hypothesis, we used a novel task to model biased, risk-averse decision-making in rats. Animals chose between a "safe" lever, which guaranteed delivery of the wager, or an "uncertain" lever, which delivered either double the wager or nothing with 50:50 odds. The bet size varied from one to three sugar pellets. Although the amount at stake did not alter the options' utility, a subgroup of "wager-sensitive" rats increased their preference for the safe lever as the bet size increased, akin to risk aversion. In contrast, wager-insensitive rats slightly preferred the uncertain option consistently. Amphetamine increased choice of the uncertain option in wager-sensitive, but not in wager-insensitive rats, whereas a D 2/3 receptor antagonist decreased uncertain lever choice in wager-insensitive rats alone. Micro-PET and autoradiography using [ 11 C]raclopride confirmed a strong correlation between high wager sensitivity and low striatal D 2/3 receptor density. These data suggest that the propensity for biased decision-making under uncertainty is influenced by striatal D 2/3 receptor expression, and provide novel support for the hypothesis that susceptibility to chemical and behavioral addictions may share a common neurobiological basis.

Modulation of risk/reward decision making by dopaminergic transmission within the basolateral amygdala

“…From these findings, it is tempting to speculate that individual differences in riskier vs risk-averse patterns of decision making and corresponding differences in sensitivity to nonrewarded choices may be driven in part by variations in basal levels of D2 receptor activity within the BLA. This idea is in keeping with recent reports that individual differences in decision making under conditions of reward uncertainty are correlated to striatal D 2 receptor density, with lower levels of these receptors associated with greater sensitivity to how reward magnitudes modified choice biases (Cocker et al 2012). The present findings suggest that within the BLA, lower levels of D 2 receptor activity may be associated with reduced sensitivity to negative feedback.…”

Consequences of Adolescent Ethanol Consumption on Risk Preference and Orbitofrontal Cortex Encoding of Reward

“…This is an important departure from prior iterations of this task (Cocker et al, 2012;Nasrallah et al, 2009), which have relied on a step-wise reduction in the probability of risky reward across sessions. Our version of the task reduces the potential role of impaired behavioral flexibility on task performance.…”

Dopaminergic modulation of the trade-off between probability and time in economic decision-making

“…Previous work has also shown that acute administration of dopamine antagonists effectively modified reward related behaviors such as gambling (Tremblay et al, 2010) and instrumental learning (Eisenegger et al, 2014;Pessiglione et al, 2006). In rats decision-making under uncertainty was influenced by a striatal D2/3 receptor antagonist, increasing risk aversion (Cocker et al, 2012;St Onge and Floresco, 2009). A proposed mechanism for these effects has been to consider dopamine a neurotransmitter driving motivation towards rewards (Berridge et al, 2009).…”