Low Dopamine D2/D3 Receptor Availability is Associated with Steep Discounting of Delayed Rewards in Methamphetamine Dependence

Abstract

Background: Individuals with substance use disorders typically exhibit a predilection toward instant gratification with apparent disregard for the future consequences of their actions. Indirect evidence suggests that low dopamine D2-type receptor availability in the striatum contributes to the propensity of these individuals to sacrifice long-term goals for short-term gain; however, this possibility has not been tested directly. We investigated whether striatal D2/D3 receptor availability is negatively correlated with the preference for smaller, more immediate rewards over larger, delayed alternatives among research participants who met DSM-IV criteria for methamphetamine (MA) dependence.

Methods: Fifty-four adults (n = 27 each: MA-dependent, non-user controls) completed the Kirby Monetary Choice Questionnaire, and underwent positron emission tomography scanning with [(18)F]fallypride.

Results: MA users displayed steeper temporal discounting (p = 0.030) and lower striatal D2/D3 receptor availability (p < 0.0005) than controls. Discount rate was negatively correlated with striatal D2/D3 receptor availability, with the relationship reaching statistical significance in the combined sample (r = -0.291, p = 0.016) and among MA users alone (r = -0.342, p = 0.041), but not among controls alone (r = -0.179, p = 0.185); the slopes did not differ significantly between MA users and controls (p = 0.5).

Conclusions: These results provide the first direct evidence of a link between deficient D2/D3 receptor availability and steep temporal discounting. This finding fits with reports that low striatal D2/D3 receptor availability is associated with a higher risk of relapse among stimulant users, and may help to explain why some individuals choose to continue using drugs despite knowledge of their eventual negative consequences. Future research directions and therapeutic implications are discussed.

Keywords: addiction; delay discounting; dopamine; impulsivity; positron emission tomography.

Figure 1.

Regression lines illustrate correlations between delay discounting [represented as the natural log of each individual’s discount rate; ln(k)] and striatal dopamine D₂/D₃ receptor availability (indexed by [¹⁸F]fallypride non-displaceable binding potential [BP_ND], unadjusted) in whole striata of methamphetamine (MA) users and non-user controls. Pearson product-moment correlation coefficients are shown (r values).

Figure 2.

Regression lines illustrate correlations between delay discounting [represented as the natural log of each individual’s discount rate; ln(k)] and striatal dopamine D₂/D₃ receptor availability (indexed by [¹⁸F]fallypride non-displaceable binding potential [BP_ND], unadjusted) in the striatal functional subdivisions of methamphetamine (MA) users and non-user controls. Pearson product-moment correlation coefficients are shown (r values).