Exploring the Role of the Ser9Gly (rs6280) Dopamine D3 Receptor Polymorphism in Nicotine Reinforcement and Cue-elicited Craving

Overview

Journal Sci Rep

Specialty Science

Date 2020 Mar 7

PMID 32139730

Citations 9

Authors

Chidera C Chukwueke

William J Kowalczyk

Patricia Di Ciano

Marie Gendy

Richard Taylor

Stephen J Heishman

Bernard Le Foll

Affiliations

Soon will be listed here.

Abstract

Preclinical studies show that the dopamine D3 receptor (D3R) is involved in the reinstatement of drug seeking and motivation for drugs of abuse. A D3R gene variant, Ser9Gly (rs6280) has been linked to nicotine dependence, yet the mechanisms underlying its involvement in nicotine dependence is unclear. This study investigated the relationship between the Ser9Gly variant and measures of both nicotine reinforcement and cue-elicited craving. Phenotypes of smoking behaviors were assessed in genetically grouped (Glycine vs. No Glycine carriers) current smokers (n = 104, ≥ 10 cigarettes per day). Laboratory measures included a forced choice session (to measure reinforcement of nicotine containing vs. denicotinized cigarettes), and a cue-reactivity session (to measure smoking cues vs. neutral cues elicited craving). The forced choice procedure revealed that subjective ratings were significantly higher in response to nicotinized compared to denicotinized cigarettes; however the Ser9Gly variant did not influence this effect. By comparison, smoking cues elicited greater craving over time compared to neutral cues, and Glycine carriers of the Ser9Gly D3R variant seem to experience a significant blunted cue-elicited craving effect. Results support D3R involvement in nicotine cue reactivity. However, more research is needed to reveal how this gene variant modulates various aspects of nicotine dependence.

Citing Articles

The association of gene polymorphisms of adenosine and dopamine receptors with the response to caffeine citrate treatment in infants with apnea of prematurity: a prospective nested case-control study.

Xie J, Zhuang W, Zhu Y, Zheng Z, Huang Y, Ma S Ital J Pediatr. 2024; 50(1):225.

PMID: 39468580 PMC: 11520374. DOI: 10.1186/s13052-024-01776-w.

Epistasis in neurotransmitter receptors linked to posttraumatic stress disorder and major depressive disorder comorbidity in traumatized Chinese.

Xu L, Zhang J, Yang H, Cao C, Fang R, Liu P Front Psychiatry. 2024; 15:1257911.

PMID: 38487579 PMC: 10937445. DOI: 10.3389/fpsyt.2024.1257911.

Pharmacokinetic differences in nicotine and nicotine salts mediate reinforcement-related behavior: an animal model study.

Han P, Jing X, Han S, Wang X, Li Q, Zhang Y Front Neurosci. 2023; 17:1288102.

PMID: 38033549 PMC: 10687399. DOI: 10.3389/fnins.2023.1288102.

Dopamine DRD2 and DRD3 Polymorphisms Involvement in Nicotine Dependence in Patients with Treatment-Resistant Mental Disorders.

Del Casale A, Paolini M, Gentile G, Borro M, Zocchi C, Fiasche F J Pers Med. 2022; 12(4).

PMID: 35455685 PMC: 9033085. DOI: 10.3390/jpm12040565.

Tobacco and nicotine use.

Le Foll B, Piper M, Fowler C, Tonstad S, Bierut L, Lu L Nat Rev Dis Primers. 2022; 8(1):19.

PMID: 35332148 DOI: 10.1038/s41572-022-00346-w.

References

Warren G, Alberg A, Kraft A, Cummings K . The 2014 Surgeon General's report: "The health consequences of smoking--50 years of progress": a paradigm shift in cancer care. Cancer. 2014; 120(13):1914-6. PMC: 5928784. DOI: 10.1002/cncr.28695. View

Babb S, Malarcher A, Schauer G, Asman K, Jamal A . Quitting Smoking Among Adults - United States, 2000-2015. MMWR Morb Mortal Wkly Rep. 2017; 65(52):1457-1464. DOI: 10.15585/mmwr.mm6552a1. View

Bierut L, Johnson E, Saccone N . A glimpse into the future - Personalized medicine for smoking cessation. Neuropharmacology. 2013; 76 Pt B:592-9. PMC: 3883448. DOI: 10.1016/j.neuropharm.2013.09.009. View

Koob G, Volkow N . Neurobiology of addiction: a neurocircuitry analysis. Lancet Psychiatry. 2016; 3(8):760-773. PMC: 6135092. DOI: 10.1016/S2215-0366(16)00104-8. View

Le Foll B, Gallo A, Le Strat Y, Lu L, Gorwood P . Genetics of dopamine receptors and drug addiction: a comprehensive review. Behav Pharmacol. 2009; 20(1):1-17. DOI: 10.1097/FBP.0b013e3283242f05. View

Sokoloff P, Le Foll B . The dopamine D3 receptor, a quarter century later. Eur J Neurosci. 2016; 45(1):2-19. DOI: 10.1111/ejn.13390. View

Ross J, Corrigall W, Heidbreder C, Lesage M . Effects of the selective dopamine D3 receptor antagonist SB-277011A on the reinforcing effects of nicotine as measured by a progressive-ratio schedule in rats. Eur J Pharmacol. 2007; 559(2-3):173-9. DOI: 10.1016/j.ejphar.2007.01.004. View

Pak A, Ashby Jr C, Heidbreder C, Pilla M, Gilbert J, Xi Z . The selective dopamine D3 receptor antagonist SB-277011A reduces nicotine-enhanced brain reward and nicotine-paired environmental cue functions. Int J Neuropsychopharmacol. 2006; 9(5):585-602. PMC: 3732043. DOI: 10.1017/S1461145706006560. View

Le Foll B, Goldberg S . Control of the reinforcing effects of nicotine by associated environmental stimuli in animals and humans. Trends Pharmacol Sci. 2005; 26(6):287-93. DOI: 10.1016/j.tips.2005.04.005. View

10.

Zerbino D, Achuthan P, Akanni W, Amode M, Barrell D, Bhai J . Ensembl 2018. Nucleic Acids Res. 2017; 46(D1):D754-D761. PMC: 5753206. DOI: 10.1093/nar/gkx1098. View

11.

Lundstrom K, Turpin M . Proposed schizophrenia-related gene polymorphism: expression of the Ser9Gly mutant human dopamine D3 receptor with the Semliki Forest virus system. Biochem Biophys Res Commun. 1996; 225(3):1068-72. DOI: 10.1006/bbrc.1996.1296. View

12.

Jeanneteau F, Funalot B, Jankovic J, Deng H, Lagarde J, Lucotte G . A functional variant of the dopamine D3 receptor is associated with risk and age-at-onset of essential tremor. Proc Natl Acad Sci U S A. 2006; 103(28):10753-8. PMC: 1502303. DOI: 10.1073/pnas.0508189103. View

13.

Vandenbergh D, OConnor R, Grant M, Jefferson A, Vogler G, Strasser A . Dopamine receptor genes (DRD2, DRD3 and DRD4) and gene-gene interactions associated with smoking-related behaviors. Addict Biol. 2007; 12(1):106-16. DOI: 10.1111/j.1369-1600.2007.00054.x. View

14.

Higgins S, Heil S, Sigmon S, Tidey J, Gaalema D, Hughes J . Addiction Potential of Cigarettes With Reduced Nicotine Content in Populations With Psychiatric Disorders and Other Vulnerabilities to Tobacco Addiction. JAMA Psychiatry. 2017; 74(10):1056-1064. PMC: 5710465. DOI: 10.1001/jamapsychiatry.2017.2355. View

15.

Higgins S, Heil S, Sigmon S, Tidey J, Gaalema D, Stitzer M . Response to varying the nicotine content of cigarettes in vulnerable populations: an initial experimental examination of acute effects. Psychopharmacology (Berl). 2016; 234(1):89-98. PMC: 5203959. DOI: 10.1007/s00213-016-4438-z. View

16.

Balter L, Good K, Barrett S . Smoking cue reactivity in current smokers, former smokers and never smokers. Addict Behav. 2015; 45:26-9. DOI: 10.1016/j.addbeh.2015.01.010. View

17.

Garcia-Rodriguez O, Weidberg S, Gutierrez-Maldonado J, Secades-Villa R . Smoking a virtual cigarette increases craving among smokers. Addict Behav. 2013; 38(10):2551-4. DOI: 10.1016/j.addbeh.2013.05.007. View

18.

Jenks R, Higgs S . Reactivity to smoking- and food-related cues in currently dieting and non-dieting young women smokers. J Psychopharmacol. 2010; 25(4):520-9. DOI: 10.1177/0269881109359093. View

19.

Doran N . Sex differences in smoking cue reactivity: craving, negative affect, and preference for immediate smoking. Am J Addict. 2014; 23(3):211-7. DOI: 10.1111/j.1521-0391.2014.12094.x. View

20.

Gendy M, Di Ciano P, Kowalczyk W, Barrett S, George T, Heishman S . Testing the PPAR hypothesis of tobacco use disorder in humans: A randomized trial of the impact of gemfibrozil (a partial PPARα agonist) in smokers. PLoS One. 2018; 13(9):e0201512. PMC: 6160014. DOI: 10.1371/journal.pone.0201512. View