Skip to main content

Advertisement

SpringerLink
Log in

Dopamine D4 receptor polymorphism modulates cue-elicited heroin craving in Chinese

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

Subjective craving, which contributes to the continuation of drug use in active abuser and the occurrence of relapse in detoxified abusers, is considered to be a central phenomenon in addiction. Dopamine pathway has been implicated in the mechanism underlying the cue-elicited craving for a variety of addictive substances.

Objectives

The objective of this study was to test the hypothesis that heroin addicts carrying D4 dopamine receptor gene (DRD4) variable number tandem repeat (VNTR) long type allele would have higher craving after exposure to a heroin-related cue.

Materials and methods

Craving was induced by a series of exposure to neutral and heroin-related cue and were assessed in a cohort of Chinese heroin abusers (n=420) recruited from the Voluntary Drug Dependence Treatment Center at Shanghai.

Results

Significantly stronger cue-elicited heroin craving was found in individuals carrying DRD4 VNTR long type allele than the non-carriers (F=31.040, p<0.001). As for baseline craving and mean change in craving responding to neutral stimuli, no significance was found (1.06±0.34 vs 1.07±0.36, F=0.067, p =0.797 and 0.42±0.34 vs 0.45±0.37, F=0.277, p=0.599, respectively).

Conclusions

The results of our study suggest that DRD4 VNTR polymorphism contributes to cue-elicited craving in heroin dependence, indicating DRD4 VNTR represents one of potential genetic risk factors for cue-induced craving.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Asghari V, Sanyal S, Buchwaldt S, Paterson A, Jovanovic V, Van Tol HH (1995) Modulation of intracellular cyclic AMP levels by different human dopamine D4 receptor variants. J Neurochem 65:1157–1165

    PubMed  CAS  Google Scholar 

  • Bhaduri N, Das M, Sinha S, Chattopadhyay A, Gangopadhyay PK, Chaudhuri K, Singh M, Mukhopadhyay K (2006) Association of dopamine D4 receptor (DRD4) polymorphisms with attention deficit hyperactivity disorder in Indian population. Am J Med Genet 141:61–66

    Article  Google Scholar 

  • Dackis CA, O’Brien CP (2001) Cocaine dependence: a disease of the brain’s reward centers. J Subst Abuse Treat 21:111–117

    Article  PubMed  CAS  Google Scholar 

  • Di Chiara G, North RA (1992) Neurobiology of opiate abuse. Trends Pharmacol Sci 13:185–193

    Article  PubMed  Google Scholar 

  • Duaux E, Krebs MO, Loo H, Poirier MF (2000) Genetic vulnerability to drug abuse. Eur Psychiatr 15:109–114

    Article  CAS  Google Scholar 

  • Erblich J, Lerman C, Self DW et al (2004) Stress-induced cigarette craving: effects of the DRD2 TaqIRFLP and SLC6A3 VNTR polymorphism. T Pharmacogenomics J 4:102–109

    Article  CAS  Google Scholar 

  • Erblich J, Lerman C, Self DW, Diaz GA, Bovbjerg DH (2005) Effects of dopamine D2 receptor (DRD2) and transporter (SLC6A3) polymorphisms on smoking cue-induced cigarette craving among African-American smokers. Mol Psychiatry 10:407–414

    Article  PubMed  CAS  Google Scholar 

  • Faraone SV, Doyle AE, Mick E, Biederman J (2001) Meta-analysis of the association between the 7-repeat allele of the dopamine D4 receptor gene and attention deficit hyperactivity disorder. Am J Psychiatry 158:1052–1057

    Article  PubMed  CAS  Google Scholar 

  • Feldpausch DL, Needham LM, Stone MP, Althaus JS, Yamamoto BK, Svensson KA, Merchant KM (1998) The role of dopamine D4 receptor in the induction of behavioral sensitization to amphetamine and accompanying biochemical and molecular adaptions. J Pharmacol Exp Ther 286:497–508

    PubMed  CAS  Google Scholar 

  • Franke P, Nothen MM, Wang T, Knapp M, Lichtermann D, Neidt H, Sander T, Propping P, Maier W (2000) DRD4 exon III VNTR polymorphism-susceptibility factor for heroin dependence? Results of a case-control and a family-based association approach. Mol Psychiatry 5:101–104

    Article  PubMed  CAS  Google Scholar 

  • Gelernter J, Kennedy JL, van Tol HH, Civelli O, Kidd KK, Genomics. (1992) The D4 dopamine receptor (DRD4) maps to distal 11p close to HRAS. Genomics 13:208–210

    Article  PubMed  CAS  Google Scholar 

  • Gelernter J, Kranzler H, Coccaro E, Siever L, New A, Mulgrew CL (1997) D4 dopamine receptor. DRD4 alleles and novelty seeking in substance-dependence, personality-disorder, and control subjects. Am J Hum Genet 61:1144–1152

    Article  PubMed  CAS  Google Scholar 

  • Grady DL, Chi HC, Ding YC, Smith M, Wang E, Schuck S, Flodman P, Spence MA, Swanson JM, Moyzis PK (2003) High prevalence of rare dopamine receptor D4 alleles in children diagnosed with attention-deficit hyperactivity disorder. Mol Psychiatry 8:536–545

    Article  PubMed  CAS  Google Scholar 

  • Grove WM, Eckert ED, Heston L, Bouchard TJ Jr, Segal N, Lykken DT (1990) Heritability of substance abuse and antisocial behavior: a study of monozygotic twins reared apart. Biol Psychiatry 27:1293–1304

    Article  PubMed  CAS  Google Scholar 

  • Hawi Z, Segurado R, Conroy J, Sheehan K, Lowe N, Kirley A, Shields D, Fitzgerald M, Gallagher L, Gill M (2005) Preferential transmission of paternal alleles at risk genes in attention-deficit/hyperactivity disorder. Am J Hum Genet 77:958–965

    Article  PubMed  CAS  Google Scholar 

  • Hutchison KE, McGeary J, Smolen A, Bryan A, Swift RM (2002a) The DRD4 VNTR polymorphism moderates craving after alcohol consumption. Health Psychol 21:139–146

    Article  PubMed  Google Scholar 

  • Hutchison KE, LaChance H, Niaura R et al (2002b) The DRD4 VNTR polymorphism influences reactivity to smoking cues. J Abnorm Psychology 111:134–143

    Article  Google Scholar 

  • Imlah N (1989) Addiction: substance abuse and dependency. Sigma, Cheshire, pp 120–124

    Google Scholar 

  • Kotler M, Cohen H, Segman R, Gritsenko I, Nemanov LM, Lerer B, Kramer L, Zer-Zion M, Kletz I, Ebstein RP (1997) Excess dopamine D4 (DRD4) exon seven repeat alletles in opioid-dependent subjects. Mol Psychiatry 2:251–254

    Article  PubMed  CAS  Google Scholar 

  • Koob GF, Nestler EJ (1997) The neurobiology of drug addiction. J Neuropsychiatry Clin Neurosci 9:482–497

    PubMed  CAS  Google Scholar 

  • Lerman C, Swan GE (2002) Non-replication of genetic association studies: is DAT all, folks? Nicotine Tob Res 4:247–249

    Article  PubMed  Google Scholar 

  • Lichter JB, Barr CL, Kennedy JL et al (1993) A hypervariable segment in the human dopamine receptor D4 (DRD 4 ) gene. Hum Mol Genet 2:767–773

    Article  PubMed  CAS  Google Scholar 

  • Li TK (2000) Pharmacogenetics of responses to alcohol and genes that influence alcohol drinking. J Stud Alcohol 61:5–12

    PubMed  CAS  Google Scholar 

  • Li T, Xu K, Deng H, Gai G, Liu J, Liu X, Wang R, Xiang X, Zhao JM, Murray RM, Sham PC, Collier DA (1997) Association analysis of the dopamine D4 gene exon VNTR and heroin abuse in Chinese subjects. Mol Psychiatry 2:413–416

    Article  PubMed  CAS  Google Scholar 

  • Li T, Zhu ZH, Liu X, Hu X, Zhao J, Sham PC, Collier DA (2000) Association analysis of polymorphisms in the DRD4 gene and heroin abuse in Chinese subjects. Am J Med Genet 96:616–621

    Article  PubMed  CAS  Google Scholar 

  • Lu L, Xu NJ, Ge X, Yue W, Su WJ, Pei G, Ma L (2002) Reactivation of morphine conditioned place preference by drug priming: role of environmental cues and sensitization. Psychopharmacology 159:125–132

    Article  PubMed  CAS  Google Scholar 

  • Nestler EJ, Aghajanian GK (1997) Molecular and cellular basis of addiction. Science 278:58–63

    Article  PubMed  CAS  Google Scholar 

  • Rees VW, Heather N (1995) Individual differences and cue reactivity. In: Drummold DC, Tiffany ST, Glautier S, Remington B (eds). Addictive behavior: cue exposure theory and practice. Wiley, Chichester, pp 99–118

    Google Scholar 

  • Robin TW, Everitt BJ (1999) Drug addiction: bad habits add up. Nature 398:567–570

    Article  Google Scholar 

  • Robinson TE, Berridge KC (1993) The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Brain Res Rev 18:247–291

    Article  PubMed  CAS  Google Scholar 

  • Robinson TE, Berridge KC (2000) The psychology and neurobiology of addiction: an attention-sensitization view. Addiction 95:S91–S117

    Article  PubMed  Google Scholar 

  • Sayette MA, Shiffman S, Tiffany ST, Niaura RS, Martin CS, Shadel WG (2000) The measurement of drug craving. Addiction 95:S189–S210

    Article  PubMed  Google Scholar 

  • Shiffman S, Shadel WG, Niaura R, Moise KA, Jorenby DE, Ryan CF, Ferguson CL (2003) Efficacy of acute administration of nicotine gum in relief of cue-provoked cigarette craving. Psychopharmacology 166:343–350

    PubMed  CAS  Google Scholar 

  • Schuckit MA (1998) Biological, psychological and environmental predictors of the alcoholism risk: a longitudinal study. J Stud Alcohol 59:485–494

    PubMed  CAS  Google Scholar 

  • Self DW (1998) Neural substrates of drug craving and relapse in drug addiction. Ann Med 30:379–389

    Article  PubMed  CAS  Google Scholar 

  • Self DW, Barnhart WJ, Lehman DA, Nestler EJ (1996) Opposite modulation of cocaine-seeking behavior by D1- and D2-like dopamine receptor agonists. Science 271:1586–1589

    Article  PubMed  CAS  Google Scholar 

  • Swanson J, Deutsch C, Cantwell D, Posner M, Kennedy J, Barr C, Moyzis R, Schuck S, Foldman P, Spence MA (2001) Genes and attention-deficit hyperactivity disorder. Clinical Neuroscience Research 1:207–216

    Article  CAS  Google Scholar 

  • Van Tol HH, Bunzow JR, Guan HC, Sunahara RK, Seeman P, Niznik HB, Civelli O (1991) Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. Nature 350:610–614

    Article  PubMed  Google Scholar 

  • Van Tol HH, Wu CM, Guan HC, Ohara K, Bunzow JR, Civelli O, Kennedy J, Seeman P, Niznik HB, Jovanovic V (1992) Multiple dopamine D4 receptor variants in the human population. Nature 358:149–152

    Article  PubMed  Google Scholar 

  • Wang E, Ding YC, Flodman P, Kidd JR, Kidd KK, Grady DL, Ryder OA, Spence MA, Swanson JM, Moyzis RK (2004) The genetic architecture of selection at the human dopamine receptor D4 (DRD4) gene locus. Am J Hum Genet 74:931–944

    Article  PubMed  CAS  Google Scholar 

  • Wise RA (1988) The neurobiological of craving: implications for the understanding and treatment of addiction. J Abnorm Psychology 97:118–132

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Huashan Hospital affiliated to Fudan University, Shanghai, 200040, China

    Chunhong Shao

  2. State Key Laboratory of Genetic Engineering and Center for Anthropological Studies, School of Life Sciences and Morgan-Tan International Center for Life Sciences, Fudan University, Shanghai, 200433, China

    Yifeng Li, Dandan Zhang, Ling Lin & Li Jin

  3. Shanghai Mental Health Center, Shanghai, 200030, China

    Kaida Jiang, Yifeng Xu & Min Zhao

  4. Shanghai Drug Abuse Treatment Center, Shanghai, 200030, China

    Qiuying Wang & Min Zhao

  5. University of Cincinnati College of Medicine, Cincinnati, 670056, USA

    Li Jin

  6. State Key Laboratory of Genetic Engineering and Center for Anthropological Studies, School of Life Science and Morgan-Tan International Center for Life Science, Fudan University, Shanghai, 200433, China Center for Genome Information, Department of Environmental Health, University of Cincinnati College of Medicine, 3223 Eden Avenue, P.O. Box 670056, Cincinnati, OH, 45267-0056, USA

    Li Jin

Authors
  1. Chunhong Shao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yifeng Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kaida Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Dandan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yifeng Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ling Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Qiuying Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Min Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Li Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Min Zhao or Li Jin.

Additional information

Li Jin and Min Zhao contributed to the work equally. Chunhong Shao and Yifeng Li contributed to the work equally.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shao, C., Li, Y., Jiang, K. et al. Dopamine D4 receptor polymorphism modulates cue-elicited heroin craving in Chinese. Psychopharmacology 186, 185–190 (2006). https://doi.org/10.1007/s00213-006-0375-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-006-0375-6

Keywords

Search

Navigation