Irrational choice under uncertainty correlates with lower striatal D(2/3) receptor 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.

Figure 1.

Schematic diagram showing the trial structure for the betting task. The rat initiated each trial by making a nosepoke response at the illuminated food tray. The tray light was then extinguished, and 1–3 response holes were illuminated, signaling the size of the bet or wager (1–3 sugar pellets). A nosepoke response at an illuminated aperture turned off the light inside it. Once all the aperture lights had been extinguished in this manner, two levers were presented to the rat. Selection of the uncertain lever resulted in a 50:50 chance of receiving either double the wager or nothing, whereas selection of the safe lever always lead to delivery of the wager. The trial was scored as a choice omission if the rat failed to choose one of the levers within 10 s. Likewise, if the rat failed to respond at each illuminated response hole within 10 s, the trial was scored as a hole omission.

Figure 2.

Rats exhibit individual differences in preference for the uncertain reward, and this determines the response to amphetamine and eticlopride. a, Wager-sensitive rats shifted their preference as the bet size increased, whereas the choice pattern of wager-insensitive rats did not change. b, The degree of wager sensitivity shown by each rat, as indicated by the gradient (m) of the line obtained by plotting choice of the uncertain lever against bet size. c, d, Amphetamine increased choice of the uncertain option in wager-sensitive (c) but not wager-insensitive rats (d). e, f, In contrast, eticlopride had no effect in wager-sensitive rats (e), but decreased uncertain choice in wager-insensitive animals (f). Data shown are mean ± SEM.

Figure 3.

Lack of effect of the D₁ receptor antagonist SCH 23390 on choice behavior. SCH 23390 did not alter preference for the uncertain lever at any bet size in either wager-sensitive (a) or wager-insensitive (b) rats. Data shown are mean ± SEM.

Figure 4.

Wager sensitivity correlates with striatal D_2/3 receptor density. a, b, Striatal D_2/3 receptor availability, measured by (a) PET as a tissue input BP_ND and (b) autoradiography using [¹¹C]raclopride, predicts wager sensitivity as estimated by coefficient m (high negative values indicate high wager sensitivity). c, d, D_2/3 receptor availability in a wager-insensitive animal as measured by PET and autoradiography respectively. e, f, The same data from a wager-sensitive rat. Data are shown on the same scale. The binding measurements obtained from PET and autoradiography analyses were strongly correlated (r² = 0.60, p = 0.02).

Figure 5.

Null relationship between the degree of wager-sensitivity and [³H]SCH 23390 binding to D₁ receptors in the striatum. Wager-sensitivity could not be predicted from striatal D₁ receptor binding.