Skip to main content

Advertisement

Log in

Variants in GABBR1 Gene Are Associated with Methamphetamine Dependence and Two Years’ Relapse after Drug Rehabilitation

  • ORIGINAL ARTICLE
  • Published:
Journal of Neuroimmune Pharmacology Aims and scope Submit manuscript

Abstract

Methamphetamine (MA) use disorder is a growing global health challenge marked by a steady increase worldwide. GABAergic system plays an important role in the mechanism of drug dependence, however few studies about the association between methamphetamine use disorder and genes in GABAergic system. Concerning GABBR1 gene which encoding the GABAB receptor subunit 1 is an important regulator in the GABAergic system. The aim of the study is to explore whether GABBR1 gene play a role in methamphetamine dependence and relapse after rehabilitation. Three single nucleotide polymorphisms (SNPs, rs2076483, rs29221, rs715044) of the GABBR1 gene were genotyped in 791 participants with MA use disorder and 448 healthy controls. The distribution of genotypes and alleles of the three SNPs between the two groups and their subgroups (dependence and abuse) was been analyzed. The multivariate logistic model was used to identify factors associate with relapse of MA use disorder during the following 2 years after drug rehabilitation. It was found that the C allele frequency of rs715044 of the GABBR1 gene was associated with MA use disorder and MA dependence. The CGA (rs2076483- rs29221- rs715044) was negatively associated with MA use disorder. The drug use years and rs29221 GG genotype were associated with relapse during the following 2 years after drug rehabilitation. GABBR1 gene may be associated with the susceptibility for MA use disorder and relapse and it indicates that the GABAergic system may play a role in the MA use disorder.

GABBR1 gene may be associated with the susceptibility for MA use disorder and relapse and it indicates that the GABAergic system may play a role in the MA use disorder.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  • APA (2013) Substance-related and addictive disorders. Diagnostic and statistical manual of mental disorders: DSM-V. American Psychiatric Association

  • Arai S, Takuma K, Mizoguchi H, Ibi D, Nagai T, Takahashi K, Kamei H, Nabeshima T, Yamada K (2008) Involvement of pallidotegmental neurons in methamphetamine- and MK-801-induced impairment of prepulse inhibition of the acoustic startle reflex in mice: reversal by GABAB receptor agonist baclofen. Neuropsychopharmacology 33:3164–3175

    Article  CAS  Google Scholar 

  • Arai S, Takuma K, Mizoguchi H, Ibi D, Nagai T, Kamei H, Kim HC, Yamada K (2009) GABAB receptor agonist baclofen improves methamphetamine-induced cognitive deficit in mice. Eur J Pharmacol 602:101–104

    Article  CAS  Google Scholar 

  • Bartoletti M, Gubellini C, Ricci F, Gaiardi M (2005) Baclofen blocks the development of sensitization to the locomotor stimulant effect of amphetamine. Behav Pharmacol 16:553–558

    Article  CAS  Google Scholar 

  • Bousman CA, Glatt SJ, Everall IP, Tsuang MT (2009) Genetic association studies of methamphetamine use disorders: a systematic review and synthesis. Am J Med Genet B Neuropsychiatr Genet 150b:1025–1049

    Article  CAS  Google Scholar 

  • Bramness JG, Rognli EB (2016) Psychosis induced by amphetamines. Curr Opin Psychiatry 29:236–241

    Article  Google Scholar 

  • Brebner K, Ahn S, Phillips AG (2005) Attenuation of d-amphetamine self-administration by baclofen in the rat: behavioral and neurochemical correlates. Psychopharmacology 177:409–417

    Article  CAS  Google Scholar 

  • Brecht ML, Herbeck D (2014) Time to relapse following treatment for methamphetamine use: a long-term perspective on patterns and predictors. Drug Alcohol Depend 139:18–25

    Article  Google Scholar 

  • Brecht ML, Anglin MD, Dylan M (2005) Coerced treatment for methamphetamine abuse: differential patient characteristics and outcomes. Am J Drug Alcohol Abuse 31:337–356

    Article  Google Scholar 

  • Caputo F, Ciminelli BM, Jodice C, Blasi P, Vignoli T, Cibin M, Zoli G, Malaspina P (2017) Alcohol use disorder and GABAB receptor gene polymorphisms in an Italian sample: haplotype frequencies, linkage disequilibrium and association studies. Ann Hum Biol 44:384–388

    Article  Google Scholar 

  • Cartier J, Farabee D, Prendergast ML (2006) Methamphetamine use, self-reported violent crime, and recidivism among offenders in California who abuse substances. J Interpers Violence 21:435–445

    Article  Google Scholar 

  • Colfax G, Guzman R (2006) Club drugs and HIV infection: a review. Clin Infect Dis 42:1463–1469

    Article  Google Scholar 

  • Courtney KE, Ray LA (2016) Clinical neuroscience of amphetamine-type stimulants: from basic science to treatment development. Prog Brain Res 223:295–310

    Article  Google Scholar 

  • Enoch MA, Zhou Z, Kimura M, Mash DC, Yuan Q, Goldman D (2012) GABAergic gene expression in postmortem hippocampus from alcoholics and cocaine addicts; corresponding findings in alcohol-naive P and NP rats. PLoS One 7:e29369

    Article  CAS  Google Scholar 

  • Enoch MA, Hodgkinson CA, Shen PH, Gorodetsky E, Marietta CA, Roy A, Goldman D (2016) GABBR1 and SLC6A1, two genes involved in modulation of GABA synaptic transmission, influence risk for alcoholism: results from three ethnically diverse populations. Alcohol Clin Exp Res 40:93–101

    Article  CAS  Google Scholar 

  • Halbout B, Quarta D, Valerio E, Heidbreder CA, Hutcheson DM (2011) The GABA-B positive modulator GS39783 decreases psychostimulant conditioned-reinforcement and conditioned-reward. Addict Biol 16:416–427

    Article  CAS  Google Scholar 

  • Hermens DF, Lubman DI, Ward PB, Naismith SL, Hickie IB (2009) Amphetamine psychosis: a model for studying the onset and course of psychosis. Med J Aust 190:S22–S25

    PubMed  Google Scholar 

  • Hillhouse MP, Marinelli-Casey P, Gonzales R, Ang A, Rawson RA (2007) Predicting in-treatment performance and post-treatment outcomes in methamphetamine users. Addiction 102(Suppl 1):84–95

    Article  Google Scholar 

  • Hsieh JH, Stein DJ, Howells FM (2014) The neurobiology of methamphetamine induced psychosis. Front Hum Neurosci 8:537

    Article  Google Scholar 

  • Jiao D, Liu Y, Li X, Liu J, Zhao M (2015) The role of the GABA system in amphetamine-type stimulant use disorders. Front Cell Neurosci 9:162

    Article  Google Scholar 

  • Jiao DL, Chen Y, Liu Y, Ju YY, Long JD, Du J, Yu CX, Wang YJ, Zhao M, Liu JG (2017) SYVN1, an ERAD E3 ubiquitin ligase, is involved in GABAAalpha1 degradation associated with methamphetamine-induced conditioned place preference. Front Mol Neurosci 10:313

    Article  Google Scholar 

  • Kaupmann K, Huggel K, Heid J, Flor PJ, Bischoff S, Mickel SJ, McMaster G, Angst C, Bittiger H, Froestl W, Bettler B (1997) Expression cloning of GABA(B) receptors uncovers similarity to metabotropic glutamate receptors. Nature 386:239–246

    Article  CAS  Google Scholar 

  • Kohnke M, Schick S, Lutz U, Kohnke A, Vonthein R, Kolb W, Batra A (2006) The polymorphism GABABR1 T1974C[rs29230] of the GABAB receptor gene is not associated with the diagnosis of alcoholism or alcohol withdrawal seizures. Addict Biol 11:152–156

    Article  Google Scholar 

  • Li MD, Mangold JE, Seneviratne C, Chen GB, Ma JZ, Lou XY, Payne TJ (2009a) Association and interaction analyses of GABBR1 and GABBR2 with nicotine dependence in European- and African-American populations. PLoS One 4:e7055

    Article  Google Scholar 

  • Li Z, Zhang Z, He Z, Tang W, Li T, Zeng Z, He L, Shi Y (2009b) A partition-ligation-combination-subdivision EM algorithm for haplotype inference with multiallelic markers: update of the SHEsis (http://analysis.bio-x.cn). Cell Res 19:519–523

    Article  CAS  Google Scholar 

  • Lin SK, Chen CK, Ball D, Liu HC, Loh EW (2003) Gender-specific contribution of the GABA(A) subunit genes on 5q33 in methamphetamine use disorder. Pharmacogenomics J 3:349–355

    Article  CAS  Google Scholar 

  • Long JD, Liu Y, Jiao DL, Wang YJ, Zan GY, Ju YY, Zhao M, Liu JG (2017) The neuroprotective effect of memantine on methamphetamine-induced cognitive deficits. Behav Brain Res 323:133–140

    Article  CAS  Google Scholar 

  • Mahmoud KF, Finnell D, Savage CL, Puskar KR, Mitchell AM (2017) A concept analysis of substance misuse to inform contemporary terminology. Arch Psychiatr Nurs 31:532–540

    Article  Google Scholar 

  • Marshall BD, Werb D (2010) Health outcomes associated with methamphetamine use among young people: a systematic review. Addiction 105:991–1002

    Article  Google Scholar 

  • McMahon RC (2001) Personality, stress, and social support in cocaine relapse prediction. J Subst Abus Treat 21:77–87

    Article  CAS  Google Scholar 

  • Moeeni M, Razaghi EM, Ponnet K, Torabi F, Shafiee SA, Pashaei T (2016) Predictors of time to relapse in amphetamine-type substance users in the matrix treatment program in Iran: a cox proportional hazard model application. BMC Psychiatry 16:265

    Article  Google Scholar 

  • Moriya Y, Kasahara Y, Sora I (2013) Genetic vulnerability of methamphetamine dependence. Nihon shinkei seishin yakurigaku zasshi 33:155–160

    CAS  PubMed  Google Scholar 

  • Nishiyama T, Ikeda M, Iwata N, Suzuki T, Kitajima T, Yamanouchi Y, Sekine Y, Iyo M, Harano M, Komiyama T, Yamada M, Sora I, Ujike H, Inada T, Furukawa T, Ozaki N (2005) Haplotype association between GABAA receptor gamma2 subunit gene (GABRG2) and methamphetamine use disorder. Pharmacogenomics J 5:89–95

    Article  CAS  Google Scholar 

  • Padgett CL, Lalive AL, Tan KR, Terunuma M, Munoz MB, Pangalos MN, Martinez-Hernandez J, Watanabe M, Moss SJ, Lujan R, Luscher C, Slesinger PA (2012) Methamphetamine-evoked depression of GABA(B) receptor signaling in GABA neurons of the VTA. Neuron 73:978–989

    Article  CAS  Google Scholar 

  • Phillips TJ, Reed C (2014) Targeting GABAB receptors for anti-abuse drug discovery. Expert Opin Drug Discovery 9:1307–1317

    Article  CAS  Google Scholar 

  • Pluddemann A, Flisher AJ, McKetin R, Parry C, Lombard C (2010) Methamphetamine use, aggressive behavior and other mental health issues among high-school students in Cape Town, South Africa. Drug Alcohol Depend 109:14–19

    Article  Google Scholar 

  • Reiber C, Ramirez A, Parent D, Rawson RA (2002) Predicting treatment success at multiple timepoints in diverse patient populations of cocaine-dependent individuals. Drug Alcohol Depend 68:35–48

    Article  Google Scholar 

  • Ribeiro AF, Correia D, Torres AA, Boas GR, Rueda AV, Camarini R, Chiavegatto S, Boerngen-Lacerda R, Brunialti-Godard AL (2012) A transcriptional study in mice with different ethanol-drinking profiles: possible involvement of the GABA(B) receptor. Pharmacol Biochem Behav 102:224–232

    Article  CAS  Google Scholar 

  • Rognli EB, Bramness JG (2015) Understanding the relationship between amphetamines and psychosis. Curr Addict Rep 2:285–292

    Article  Google Scholar 

  • Shaul O (2017) How introns enhance gene expression. Int J Biochem Cell Biol 91:145–155

    Article  CAS  Google Scholar 

  • Shi YY, He L (2005) SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Res 15:97–98

    Article  CAS  Google Scholar 

  • Terranova C, Tucci M, Di Pietra L, Ferrara SD (2014) GABA receptors genes polymorphisms and alcohol dependence: no evidence of an association in an Italian Male Population. Clin Psychopharmacol Neurosci 12:142–148

    Article  CAS  Google Scholar 

  • United Nations Office on Drugs and Crime (2017) World drug report 2017. http://www.unodc.org/wdr2017/

  • Voigt RM, Herrold AA, Riddle JL, Napier TC (2011) Administration of GABA(B) receptor positive allosteric modulators inhibit the expression of previously established methamphetamine-induced conditioned place preference. Behav Brain Res 216:419–423

    Article  CAS  Google Scholar 

  • Walker DM, Nestler EJ (2018) Neuroepigenetics and addiction. Handb Clin Neurol 148:747–765

    Article  Google Scholar 

  • Wieronska JM, Kusek M, Tokarski K, Wabno J, Froestl W, Pilc A (2011) The GABA B receptor agonist CGP44532 and the positive modulator GS39783 reverse some behavioural changes related to positive syndromes of psychosis in mice. Br J Pharmacol 163:1034–1047

    Article  CAS  Google Scholar 

  • Winterer G, Smolka M, Samochowiec J, Ziller M, Mahlberg R, Gallinat J, Rommelspacher HP, Herrmann WM, Sander T (2003) Association of EEG coherence and an exonic GABA(B)R1 gene polymorphism. Am J Med Genet B Neuropsychiatr Genet 117b:51–56

    Article  Google Scholar 

  • Wise RA (2009) Roles for nigrostriatal--not just mesocorticolimbic--dopamine in reward and addiction. Trends Neurosci 32:517–524

    Article  CAS  Google Scholar 

  • Yin X, Bizon C, Tilson J, Lin Y, Gizer IR, Ehlers CL, Wilhelmsen KC (2017) Genome-wide meta-analysis identifies a novel susceptibility signal at CACNA2D3 for nicotine dependence. Am J Med Genet B Neuropsychiatr Genet 174B:557–567

    Article  CAS  Google Scholar 

  • Zai G, King N, Wong GW, Barr CL, Kennedy JL (2005) Possible association between the gamma-aminobutyric acid type B receptor 1 (GABBR1) gene and schizophrenia. Eur Neuropsychopharmacol 15:347–352

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the National Key R&D Program of China (2017YFC1310400), National Nature Science Foundation (U1502228, 81,771,436), Program of Shanghai Academic Research Leader (17XD1403300), Shanghai Key Laboratory of Psychotic Disorders (13DZ2260500), Shanghai Municipal Health and Family Planning Commission (2017ZZ02021), Shanghai City Committee of Science and Technology project (16JC1420202) to Min Zhao and the Qihang project of Shanghai Mental Health Center (2017-QH-05) to Yan Zhao. All the authors declare no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Min Zhao.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, Y., Peng, S., Jiang, H. et al. Variants in GABBR1 Gene Are Associated with Methamphetamine Dependence and Two Years’ Relapse after Drug Rehabilitation. J Neuroimmune Pharmacol 13, 523–531 (2018). https://doi.org/10.1007/s11481-018-9802-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11481-018-9802-9

Keywords

Navigation