Heroin delay discounting and impulsivity: Modulation by DRD1 genetic variation

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. DRD3and 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.

Deprivation Has Inconsistent Effects on Delay Discounting: A Review

“…Both studies used relatively large samples (>100) of out of treatment heroin users and required a positive urinalysis to participate. Although both Stoltman et al ( 2015 ) and Moses et al ( 2019 ) found increases in delay discounting, imagined withdrawal is arguably different from experienced withdrawal. It is also unclear if the increase in discounting found in Stoltman et al ( 2015 ) and Moses et al ( 2019 ) would generalize to more traditional delay discounting tasks with larger amounts of money and longer delays.…”

“…Although both Stoltman et al ( 2015 ) and Moses et al ( 2019 ) found increases in delay discounting, imagined withdrawal is arguably different from experienced withdrawal. It is also unclear if the increase in discounting found in Stoltman et al ( 2015 ) and Moses et al ( 2019 ) would generalize to more traditional delay discounting tasks with larger amounts of money and longer delays. That is, the large effect found due to hypothetical opioid withdrawal may only be large because the task involved heroin.…”

“…Stoltman et al ( 2015 ) and Moses et al ( 2019 ) developed a hypothetical opioid deprivation model and found that delay discounting was steeper during deprived states than during satiated states. In the hypothetical withdrawal condition, participants were instructed to answer as if they were going through opioid withdrawal.…”

“…Although four of the five studies reported increases in delay discounting due to opioid deprivation, each had some limitations. Future studies could attempt to further validate and generalize the hypothetical deprivation condition described in Stoltman et al (2015) and Moses et al (2019). Once validated, the hypothetical deprivation model could be a preferable alternative to asking participants to voluntarily go through actual opioid withdrawal.…”

The Allele Frequency Variation of Autosomal 19 Short Tandem Repeat (STR) Loci in Drug Abuser: A Pilot Study

“…Additionally, internal environment changes may lead to sequence variation and increase the heterozygosity of STR loci and become a possible mechanism of drug abuse [31,32], namely, increased heterozygosity of some alleles may be a risk factor for susceptibility and recurrence [33], while the homozygous genotype of the gene reduces the risk of addiction [34,35].…”