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. 2020 May;25(3):e12777.
doi: 10.1111/adb.12777. Epub 2019 Jun 13.

Heroin delay discounting and impulsivity: Modulation by DRD1 genetic variation

Tabitha E H Moses  1 , Margit Burmeister  2 , Mark K Greenwald  1
Affiliations

Heroin delay discounting and impulsivity: Modulation by DRD1 genetic variation

Tabitha E H Moses et al. Addict Biol. 2020 May.

Abstract

Background: Dopamine D1 receptors (encoded by DRD1) are implicated in drug addiction and high-risk behaviors. Delay discounting (DD) procedures measure decisional balance between choosing smaller/sooner rewards vs larger/later rewards. Individuals with higher DD (rapid discounting) are prone to maladaptive behaviors that provide immediate reinforcement (eg, substance use). DRD1 variants have been linked with increased DD (in healthy volunteers) and opioid abuse. This study determined whether four dopaminergic functional variants modulated heroin DD and impulsivity.

Methods: Substance use, DD, and genotype data (DRD1 rs686 and rs5326, DRD3 rs6280, COMT rs4680) were obtained from 106 current heroin users. Subjects completed an array of DD choices during two imagined conditions: heroin satiation and withdrawal. Rewards were expressed as $10 heroin bag units, with maximum delayed amount of 30 bags. Delays progressively increased from 3 to 96 hours.

Results: DRD1 rs686 (A/A, n = 25; G/A, n = 56; G/G, n = 25) was linearly related to the difference in heroin DD (area under the curve; AUC) between the heroin satiation and withdrawal conditions; specifically, G/G homozygotes had a significantly smaller (satiation minus withdrawal) AUC difference score had higher drug-use impulsivity questionnaire scores, relative to A/A homozygotes, with G/A intermediate. DRD3 and COMT variants were not associated with these DD and impulsivity outcomes.

Conclusion: DRD1 rs686 modulated the difference in heroin DD score between pharmacological states and was associated with drug-use impulsivity. These data support a role of DRD1 in opioid DD and impulsive behaviors.

Keywords: DRD1; delay discounting; dopamine; heroin; impulsivity.

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Conflict of interest statement

Conflict of Interest

All authors declare no conflict of interest with respect to the conduct or content of this work.

Figures

Figure 1
Figure 1
Mean (+ 1 SEM) heroin delay discounting AUC scores during participant-imagined satiation and withdrawal pharmacological-state conditions, by DRD1 rs686 genotype and race
Figure 2
Figure 2
Mean (+ 1 SEM) change in heroin delay discounting AUC scores between pharmacological-state conditions, by DRD1 rs686 genotype and race
Figure 3
Figure 3
Mean (+ 1 SEM) heroin delay discounting indifference points in satiation and withdrawal conditions as a function of DRD1 rs686 genotype (upper row) and time course of Satiation – Withdrawal difference score for each genotype group (lower panel).
See this image and copyright information in PMC

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