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La adicción y su proceso de recompensa por medio de polimorfismos del gen del receptor D2 de dopamina: una revisión
Published online by Cambridge University Press: 12 May 2020
Resumen
Desde 1990, los estudios de asociación han acumulado sólidos datos que implican al gen del receptor D2 de dopamina (DRD2) en el alcoholismo. Específicamente, se ha asociado con el alcoholismo el alelo menor A (Al) Taql del gen del DRD2. Se ha encontrado también que el gen del DRD2 está implicado en otros trastornos por uso de sustancias, incluida la dependencia de cocaína, nicotina y opioides, y la obesidad. Además de los estudios de asociación, los estudios farmacológicos han mostrado un número reducido de receptores D2 de dopamina cerebrales en los portadores de alelos Al+ (genotipos A1A1 y A1A2), en comparación con los portadores de alelos Al- (genotipo A2A2). Por medio de varios otros enfoques, se han identificado también fenotipos diferentes en los sujetos con los alelos Al+ y Al-. Estos enfoques incluyen estudios metabólicos, neurofisiológicos, neuropsicoógicos, de personalidad, de estrés y de tratamiento. Se ha formado la hipótesis de que, en un esfuerzo por compensar las deficiencias en el sistema dopaminérgico, las personas que abusan de sustancias pueden tratar de estimular los circuitos mesocorticolímbicos del cerebro, que desde hace mucho tiempo se ha pensado que son importantes en la recompensa y el refuerzo conductuales. En efecto, una forma del gen del DRD2, el alelo Al, hace ineficaz el sistema dopaminérgico y recompensa el abuso de sustancias que aumenta los niveles de dopamina en el cerebro.
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References
Bibliografía
Adams, KMGilman, SKoeppe, RAKluin, KJBrunberg, JADede, D, et al.Neuropsychological deficits are correlated with frontal hypometabolism in positron emission tomo-graphy studies of older alcoholic patients. Alcohol Clin Exp Res 1993;17:205–10.CrossRefGoogle Scholar
Arnadéo, SAbbar, MFourcade, MI.Waksman, GLeroux, MGMedec, A, et al.D2 dopamine receptor gene and alcoholism. J Psychiatr Res 1993;27:173–9.Google Scholar
Babor, TFHofmann, MDelBoca, FKHesselbrock, VMeyer, REDolinsky, ZS, et al.Types of alcoholics: I. Evidence for an empirically derived typology based on indicators of vulnerability and severy. Arch Gen Psychatry 1992;49:599–608.CrossRefGoogle Scholar
Benjamin, JLi, LPalterson, CGreenberg, BDMurphy, DLHamer, DH.Population and familial association between the D4 dopamine receptor gene and measures of novelty seeking. Nat Genet 1996;12:81–4.CrossRefGoogle ScholarPubMed
Berman, SMNoble, EP.Reduced visuospatial performance in children with the D2 dopamine receptor Al allele. Behav Genet 1995;25:45–58.CrossRefGoogle Scholar
Berman, SMNoble, EP.The D2 dopamine receptor (DRD2) gene and family stress. Interactive effects on cognitive fiinctioning in children. Behav Genet 1997;27:33–43.CrossRefGoogle ScholarPubMed
Blum, KBraverman, EPDinardo, MJWood, RCSheridan, PJ.Prolonged P300 latency in a neuropsychiatric popula-don with the D2 dopamine receptor A1 allele. Pharmacogenetics 1994;3:313–22.CrossRefGoogle Scholar
Blum, KNoble, EPSheridan, PJFinley, OMontgomery, ARitchie, T, et al.Association of the Al allelle of the human D2 dopamine receptor gene with severe alcoholism. Alcohol 1991;8:409–16.CrossRefGoogle Scholar
Blum, KNoble, EPSheridan, PJMontgomery, ARitchie, TJagadeeswaran, P, et al.Allelic association of human dopamine D2 receptor gene in alcoholism. JAMA 1990;263:2055–60.CrossRefGoogle ScholarPubMed
Blum, KSheridan, PJWood, RCBraverman, ERChen, IJHComings, DE.Dopamine D2 receptor gene variants: Association and linkage studies in impulsive-addictive-compulsive behavior. Pharmacogenetics 1995;5:121–41.CrossRefGoogle Scholar
Bolos, AMDean, MLucase-Derse, SRamsburg, MBrown, GLGoldman, D, et al.Population and pedigree studies reveal a lack of association between the dopamine D2 receptor gene and alcoholism. JAMA 1990;264:3156–60.CrossRefGoogle ScholarPubMed
Cloninger, CR.Neurogenetic adaptive mechanisms in alcoholism. Science 1987;236:410–6.CrossRefGoogle ScholarPubMed
Cloninger, CR.D2 dopamine receptor gene is associated but not linked with alcoholism. JAMA 1991;266:1833–4.CrossRefGoogle Scholar
Comings, DEComings, BGMuhleman, DDietz, GShahbahrami, BTast, D, et al.The dopamine D2 receptor locus as a modifying gene in neuropsychiatric disorders. JAMA 1991;266:1793–1800.CrossRefGoogle ScholarPubMed
Comings, DEFerry, LBradshaw-Robinson, SBurchette, RChiu, CMuhleman, D.The dopamine D2 receptor (DRD2) gene: A genetic risk factor in smoking. Pharmacogenetics 1996;6:73–9.CrossRefGoogle ScholarPubMed
Comings, DEFlanagan, SDDietz, GMuhleman, DKnell, EGysin, R.The dopamine D2 receptor (DRD2) as a major gene in obesity and height. Biochem Med Metab Biol 1993;50:176–85.CrossRefGoogle ScholarPubMed
Comings, DEGade, RMacmurray, JPMuhleman, DPeters, WR.Genetic variants of the human obesity (OB) gene: association with body mass Index in young women, psy-chiatric sympsoms, and interaction with the dopamine D2 receptor (DRD2) gene. Mol Psychiatry 1996;1:325–35.Google ScholarPubMed
Comings, DEMuhleman, DAhn, CGysin, RFlanagan, SD.The dopamine D2 receptor gene. A genetic risk factor in substance abuse. Drug Alcohol Depend 1994;34:175–80.CrossRefGoogle ScholarPubMed
Cook, BLWang, ZWCrowe, RRHauser, RFreimer, M.Alcoholism and the D2 receptor gene. Alcohol Clin Exp Res 1992;16:806–9.CrossRefGoogle ScholarPubMed
Cook, CCHGurling, HMD.The D2 dopamine receptor gene and alcoholism: A genetic effect on the liability for alcoholism. J R Soc Med 1994;87:400–2.Google ScholarPubMed
Ebstein, RPNovick, OUmansky, RPriel, BOsher, YBlaine, D, et al.Dopamine D4 receptor (DRD4) exon III polymorphism associated with the human perso-nality trait of novelty seeking. Nat Genet 1996;12:78–80.CrossRefGoogle ScholarPubMed
Gabbay, FHDuncan, CCBird, GUhl, GRMirsky, AF.D2 dopamine receptor Taql A genotypic differences in event-related brain potentials. In: Harris, LS, ed. Problems of Drug Dependence. NIDA Research Mono-graph 162. Rockville MD: NIH, National Institute of Drug Abuse; 1996; 129.Google Scholar
Gehle, VMErwin, VG.Common quantitative trait loci for alcohol-related behaviors and CNS neurotensin measu-res: voluntary ethanol consumption. Alcohol Clin Exp Res 1998;22:40–8.Google ScholarPubMed
Geijer, TNeiman, JRydberg, UGyllander, AJohnson, ESedvall, G, et al.Dopamine D2 receptor gene polymor-phisms in Scandinavian chronic alcoholics. Eur Arch Psychiatry Clin Neursci 1994;244:26–32.CrossRefGoogle Scholar
Gelemter, JGoldman, DRisch, N.The Al allele of the D2 dopamine receptor gene and alcoholism. JAMA 1993;269:1673–7.Google Scholar
Gelemter, JO’Malley, SRisch, NKranzler, HRKrystal, JMerikangas, K, et al.No association between and allele of the D2 dopamine receptor gene (DRD2) and alcoholism. JAMA 1991;266:1801–7.CrossRefGoogle Scholar
Goldman, DDean, MBrown, GLBolos, ANTokola, RVirkkunen, M, et al.D2 dopamine receptor genotype and cerebral spinal fluid homovanillic acid, 5-hydroxyindoIe-acetic acid and 3-methoxy-4-hydroxyphenylglycol in alcoholics in Finland and the United States. Acta Psychiatr Scand 1992;86:351–7.CrossRefGoogle ScholarPubMed
Gorwood, PAdes, JFeingold, J.Are genes coding for dopamine receptors implicated in alcoholism? Eur Psychiatry 1994;9:63–9.Google Scholar
Grandy, DKLitt, MAlien, LBunzow, JRMarchionni, MMakam, H, et al.The human dopamine D2 receptor gene is located on chromosome 11 at q22-q23 and identifies a Taql RFLP. AmJ Hum Genet 1989;45:778–85.Google Scholar
Heinz, ASander, THarms, HFinckh, UKulin, SDufeu, P, et al.Lack of allelic association of dopamine DI and D2 (Taql A) receptor gene polymorphisms with reduced dopaminergic sensitivity in alcoholism. Alcohol Clin Exp Res 1996;20:1109–13.CrossRefGoogle Scholar
Hietala, JPohjalainen, THeikkila-Kallio, UWest, CSalaspuro, MSyvålahti, E.Allelic association between D2 but not DI dopamine receptor gene and alcoholism in Finland. Psychiat Genet 1997;7:19–25.CrossRefGoogle ScholarPubMed
Hill, SYLocke, JZezza, NKaplan, BNeiswanger, KSteinhauer, SR, et al.Genetic association between reduced P300 amplitude and the DRD2 dopamine receptor Al allele in children at high-risk for alcoholism. Biol Psychiatry 1998;43:40–51.CrossRefGoogle Scholar
Hitzemann, RJ.The regulation of D2 dopamine receptor expression. Mol Psychiatry 1998;3:198–203.CrossRefGoogle ScholarPubMed
Jönsson, EGNöthen, MMGustavsson, JPNeidt, HBrené, STylee, A, et al.Lack of evidence for allelic association between personality traits and dopamine D4 receptor gene polymorphism. Am J Psychiatry 1997;154:697–9.Google Scholar
Koob, GR.Drugs of abuse. Anatomy, pharmacology and function of reward pathways. Trends Pharmacol Sci 1992;13:177–84.CrossRefGoogle ScholarPubMed
Laruelle, MGelernter, JInnis, RB.D2 receptors binding potential is not affected by Taql polymorphism at the D2 receptor gene. Mol Psychiatry 1998;3:261–5.CrossRefGoogle ScholarPubMed
Lawford, BRYoung, RMRowell, JA, GibsonJN, Feeney, GFXRitchie, TL, et al.Association of the D2 dopamine receptor Al allele with alcoholism: Medical severity of alcoholism and type of Controls. Biol Psychiatry 1997;41:386–93.CrossRefGoogle Scholar
Lawford, BRYoung, RMRowell, JAQualichefski, JFletcher, BHSyndulko, K, et al.Bromocriptine in the tre-atment of alcoholics with the D2 dopamine receptor Al allele. Nat Med 1995;1:337–41.CrossRefGoogle Scholar
Maldonado, RSalardi, AValverde, OSamad, TARoques, BPBorrelli, E.Absence of opiate rewarding effects in mice lacking dopamine D2 receptors. Nature 1997;388:586–9.CrossRefGoogle ScholarPubMed
Malhotra, AKVirkunnen, MRooney, WEggert, MLinnoila, MGoldman, D.The association between the dopamine D4 receptor (DRD4) 16 amino acid repeat polymorphism and novelty seeking. Mol Psychiatry 1996;1:388–91.Google ScholarPubMed
Neiswanger, KHill, SYKaplan, BB.Association and lin-kage studies of the Taql A allele of the dopamine D2 receptor gene in samples of female and male alcoholics. Am J Med Genet 1995;60:267–71.CrossRefGoogle Scholar
Noble, EP.Alcoholism and the dopaminergic System: A review. Addict Biol 1996;1:333–48.CrossRefGoogle ScholarPubMed
Noble, EP.The D2 dopamine receptor gene: A review of association studies in alcoholism and phenotypes. Alcohol 1998;16:33–45.CrossRefGoogle ScholarPubMed
Noble, EP.The DRD2 gene, smoking, and lung cancer. J Nati Cancer Inst 1998;90:343–5.CrossRefGoogle ScholarPubMed
Noble, EPBerman, SMOzkaragoz, TZRitchie, T.Prolonged P300 latency in children with the D2 dopamine receptor Al allele. Am J Hum Genet 1994;54:658–68.Google Scholar
Noble, EPBlum, K.Alcoholism and the D2 receptor gene [letter]. JAMA 1993;270:1547.CrossRefGoogle Scholar
Noble, EPBlum, KKhalsa, MERitchie, TMontgomery, AWood, RD, et al.Allelic association of the D2 dopamine receptor gene with cocaine dependence. Drug Alcohol Depend 1993;33:271–85.CrossRefGoogle ScholarPubMed
Noble, EPBlum, KRitchie, TMontgomery, ASheridan, PJ.Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism. Arch Gen Psychiatry 1991;48:684–54.CrossRefGoogle ScholarPubMed
Noble, EPFitch, RJRitchie, TBrunner, RLZhang, XStjeor, SC, et al.The D2 dopamine receptor gene: obesity, smoking and mood. In: St. Jeor, ST, ed. Obesity Assessment. Chapman and Hall; New York: 1997;522–33.Google Scholar
Noble, EPGottschalk, LAFallon, JHRitchie, TLWu, JC.D2 dopamine receptor polymorphism and brain regional metabolism. Am J Med Genet 1997;74:162–6.3.0.CO;2-W>CrossRefGoogle Scholar
Noble, EPLawford, BRRitchie, TYoung, RMZhang, X.The D2 dopamine receptor (DRD2) gene and methado-ne treatment outeome of opioid-dependent patients. Abstr Soc. Neurosci 1998;24:770.Google Scholar
Noble, EPNoble, RERitchie, TSyndulko, KBohlman, MCNoble, LA, et al.D2 dopamine receptor gene and obesity. Int j Eating Disord 1994;15:205–17.3.0.CO;2-P>CrossRefGoogle ScholarPubMed
Noble, EPOzkaragoz, TZRitchie, TZhang, XBelin, TRSparkes, RS.D2 and D4 dopamine receptor polymor-phisms and personality. Am J Med Genet 1998;81:257–67.3.0.CO;2-E>CrossRefGoogle Scholar
Noble, EPStjeor, STRitchie, TSyndulko, KStjeor, SCFitch, RJ, et al.D2 dopamine receptor gene and cigarette smoking: A reward gene? Med Hypotheses 1994;42:257–60.CrossRefGoogle ScholarPubMed
Noble, EPSyndulko, KFitch, RJRitchie, TBohlman, MCGuth, P, et al.Taql A alleles in medically ill alcoholic and nonalcoholic patients. Alcohol Alcohol 1994;29:729–44.Google Scholar
O’Hara, BFSmith, SSBird, GPersico, AMSuarez, BKCutting, GR, et al.Dopamine D2 receptor RFLPs, haploty-pes and their association with substance use in black and Caucasian research volunteers. Hum Hered 1993;43:209–18.Google ScholarPubMed
Parsian, ATodd, RDDevor, EJO’Malley, KLSuarez, BKReich, T, et al.Alcoholism and alleles of the human D2 receptor locus: Studies of association and linkage. Arch Gen Psychiatry 1991;48:655–63.CrossRefGoogle ScholarPubMed
Pato, CNMacciardi, FPato, MTVerga, MKennedy, H.Review of the putative association of dopamine D2 receptor and alcoholism: A meta-analysis. Am J Med Genet 1993;48:78–82.CrossRefGoogle ScholarPubMed
Persico, AMBird, GGabbay, FHUhl, GR.D2 dopamine receptor gene Taql Al and B1 restriction fragment length polymorphism: Enhanced fraquencies in psychostimu-lant-preferring polysubstance abusers. Biol Psychiatry 1996;40:776–84.CrossRefGoogle Scholar
Phillips, TJBrown, KJBurkhart-Kasch, SWenger, CDKelly, MARubinstein, M, et al.Alcohol preference and sensitivity are markedly reduced in mice lacking dopamine D2 receptors. Nat Neurosci 1998;1:610–5.CrossRefGoogle ScholarPubMed
Phillips, TJCrabbe, JCMetten, PBelknap, JK.Localization of genes affecting alcohol drinking in mice. Alcohol Clin Exp Res 1994;18:931–43.CrossRefGoogle ScholarPubMed
Phillips, TJHuson, MGwazdon, CBurkhart-Kasch, SShen, EH.Effects of acute and repeated ethanol exposu-res on the locomotor activity of RXD recombinant inbred mice. Alcohol Clin Exp Res 1995;19:269–78.CrossRefGoogle Scholar
Pohjalainen, TRinne, JONågren, KLehikoinen, PAnttila, KSyvalahti, EKG, et al.Tire Al allele of the human D2 dopamine receptor gene predicts low D2 receptor availa-bility in healthy volunteers. Mol Psychiatiy 1998;3:256–60.CrossRefGoogle Scholar
Smith, SSO’Hara, BFPersico, AMGorelick, DANewlin, DBVlahov, D, et al.Genetic vulnerability in drug abuse: The dopamine D2 receptor Taql B RFLP is more frequent in polysubstance abusers. Arch Gen Psychiatry 1992;49:723–7.CrossRefGoogle Scholar
Spitz, MRShi, HYang, FHudmon, KSJiang, HChamberlain, RM, et al.Case-control study of the D2 dopamine receptor gene and smoking status in lung Cancer patients. J Nati Cancer Inst 1998;90:358–63.CrossRefGoogle ScholarPubMed
Suarez, BKParsian, AHampe, CLTodd, RDReich, TCloninger, CR.Linkage disequilibria and the D2 dopamine receptor locus (DRD2) in alcoholics and Controls. Genomics 1994;19:12–20.CrossRefGoogle ScholarPubMed
Tarantino, LMMcClearn, GERodríguez, LAPlomin, R.Confirmation of quantitative trait loci for alcohol pre-ference in mice. Alcohol Clin Exp Res 1998;22:1099–105.CrossRefGoogle ScholarPubMed
Thompson, JThomas, NSingleton, APiggott, MLloyd, SPerry, CM, et al.D2 dopamine receptor gene (DRD2) Taql A polymorphism: reduced dopamine D2 receptor binding in the human striatum associated with the Al allele. Pharmacogenetics 1997;7:479–84.CrossRefGoogle Scholar
Turner, EEwing, JShilling, PSmith, TLIrwin, MSchuckit, M, et al.Lack of association between an RFLP near the D2 dopamine receptor gene and severe alcoholism. Biol Psychiatry 1992;31:285–90.CrossRefGoogle ScholarPubMed
Uhl, GBlum, KNoble, ESmith, S.Substance abuse vulnerability and D2 receptor gene. Trends Neurosci 1993;16:83–8.CrossRefGoogle Scholar
Volkow, NDFowler, JBWang, GJHitzemann, RLogan, JSchyler, DJ, et al.Decreased dopamine D2 receptor avai-lability is associated with reduced frontal metabolism in cocaine abusers. Synapse 1993;14:169–77.CrossRefGoogle Scholar
Volkow, NDHitzemann, RWang, GJFowler, JSWolf, APDewey, SL, et al.Long-term frontal brain metabolism changes in cocaine abusers. Synapse 1992;11:184–90.CrossRefGoogle ScholarPubMed
Wik, GBorg, SSjogren, IWiesel, FABloomquist, GBorg, J, et al.PET determination of regional cerebral glucose metabolism in alcohol-dependent men and healthy Controls using llC-glucose. Acta Psychiatr Scand 1988;78:234–41.CrossRefGoogle Scholar
Wise, RARompre, PP.Brain dopamine and reward. Annu Rev Psychol 1989;40:191–225.CrossRefGoogle ScholarPubMed