Hostname: page-component-cd9895bd7-gbm5v Total loading time: 0 Render date: 2024-12-26T06:25:57.913Z Has data issue: false hasContentIssue false
  • English
  • Français

Disfunción dopaminérgica en el alcoholismo y la esquizofrenia: correlatos psicopatológicos y conductuales

Published online by Cambridge University Press:  12 May 2020

A. Heinz
A. Heinz*
Affiliation:
Departamento de Conducta Adictíva y Medicina de la Adicción, Instituto Central de Salud Mental, J5, 68159Mannheim, Alemania
Get access

Resumen

Se ha implicado a la disfunción de la neurotransmisión dopaminérgica central en la patogénesis de la esquizofrenia y además en la dependencia de drogas y alcohol. Diferentes drogas estimulan la liberación de la dopamina en el estriado ventral y refuerzan así el consumo. El aumento de la liberación subcortical de dopamina se ha asociado también con la patogénesis de los síntomas positivos en la esquizofrenia y puede estar conducido por una disfunción dopaminérgica prefrontal. Estos hallazgos aparentemente heterogéneos se pueden explicar por investigaciones recientes en primates no humanos. Según estos estudios, la anticipación de la recompensa pero no el consumo anticipado de la recompensa se acompaña de una liberación fásica de dopamina en el estriado y la corteza prefrontal. En el estriado, la liberación fásica de dopamina afecta ante todo a la motivación, la activación psicomotriz y el anhelo de la recompensa, mientras que en la corteza prefrontal, la estimulación dopaminérgica está implicada en la activación de la memoria operativa y la anticipación de la recompensa. En el alcoholismo, estímulos anteriormente neutrales que se han asociado con la ingesta de alcohol se pueden convertir en claves condicionadas que activen la liberación fásica de dopamina y el anhelo de la recompensa. En la esquizofrenia, la activación inducida por estrés o caótica de la liberación de dopamina puede atribuir saliencia de incentivo a estímulos por lo demás irrelevantes y, así, estar implicada en la patogénesis del estado de ánimo delirante y otros síntomas positivos. Los estudios en humanos y primates no humanos ponen de relieve el papel de la neurotransmisión dopaminérgica en la anticipación de la recompensa y su disfunción en diferentes enfermedades neuropsiquiátricas.

Keywords

hipótesis de la anhedoniadopaminaprominencia de incentivosíntomas negativossíntomaspositivos
Type
Artículo original
Information
European Psychiatry (Ed. Española) , Volume 9 , Issue 4 , May 2002 , pp. 238 - 246

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Bibliografía

Abercrombie, EDKeefe, KADiFrischia, DSZigmond, MJ.Differential effects of stress on in vivo dopamine release in striatum, nucleus accumbens, and medial frontal cortex. J Neurochem 1989;52:1655-8.CrossRefGoogle Scholar
Abi-Dargham, AKegeles, LZea-Ponce, YPrintz, DGil, RRodenhiser, J, et al.Removal of endogenous dopamine reveals elevation of D2 receptors in schizophrenia. J Nuc Med 1999;40(Suppl):30 p.Google Scholar
Balldin, JIBerggren, UCLindstedt, G.Neuroendocrine evidence for redured dopamine receptor sensitivity in alcoholism. Alcohol Clin Exp Res 1992;16:71-4.CrossRefGoogle ScholarPubMed
Berridge, KCRobinson, TE.What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Res Rev 1998;28:309-69.CrossRefGoogle ScholarPubMed
Bliss, TVPCollingridge, GL.A synaptic model of memory: long-term potentiation in the hippocampus. Nature 1993;361:31-9.CrossRefGoogle ScholarPubMed
Breier, ASu, TPSaunders, RCarson, REKolachana, BSde Bartolomeis, A, et al.Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. Proc Nad Acad Sci USA 1997;94:2569-74.CrossRefGoogle ScholarPubMed
Breier, AAdler, CMWeisenfeld, NSu, TPElman, IPicken, L, et al.Effects of NMDA antagonism on striatal dopamine release in healthy subjects: application of a novel PET approach. Synapse 1998;29:142-7.3.0.CO;2-7>CrossRefGoogle ScholarPubMed
Carboni, EAquas, ELeone, PPerezzani, LDi Chiara, G.Differential inhibitory effects of a 5-HT3 antagonist on drug-induced stimulation of dopamine release. Eur J Pharmacol 1989;164:515.CrossRefGoogle ScholarPubMed
Carlsson, A.The current status of the dopamine hypothesis of schizophrenia. Neuropsychopharmacology 1988;1:179-86.CrossRefGoogle ScholarPubMed
Chiamulera, CEpping-Jordan, MPZocchi, AMarcon, CCottiny, CTacconi, S, et al.Reinforcing and locomotor stimulant effects of cocaine are absent in mGluR5 nuil mutant mice. Nat Neurosci 2001;4:873-4.CrossRefGoogle Scholar
Conrad, C.Die beginnende Schizophreni.e. Stuttgart, New York: Thieme; 1992.Google Scholar
Cowen, MSLawrence, AJ.The role of opioid-dopamine interactions in the induction and maintenance of ethanol consumption. Prog Neuro-Psychopharmacol Biol Psychiat 1999;23:1171-212.CrossRefGoogle ScholarPubMed
Dao-Castellana, MHPailliere-Martinot, MLHantraye, PAttar Levy, DRemy, PCrouzel, C, et al.Presynaptic dopaminergic function in the striatuin of schizophrenic patients. Schizophr Res 1997;23:167-74.CrossRefGoogle ScholarPubMed
Desimone, R.Is dopamine a missing link? Nature 1995;376:549-50.CrossRefGoogle ScholarPubMed
Dettling, MHeinz, ADufeu, PRommelspacher, HGräf, KJSchmidt, LG.Dopaminergic responsivity in alcoholism: atrait-, State-or residual marker? Am j Psychiat 1995;152:1317-21.Google Scholar
Di Chiara, G.The role of dopamine in drug abuse viewed from the perspective of its role in motivation. Drug Ale Dependence 1995;38:95-137.CrossRefGoogle ScholarPubMed
Farde, LWiesel, FAHall, HHalldin, CStone-Elander, SSedvall, G.No D-2 receptor increase in PET study of schizophrenia. Arch Gen Psychiatry 1987;44:671-2.CrossRefGoogle Scholar
Finckh, URommelspacher, HKuhn, SDufeu, POtto, GHeinz, A, et al.Influence of the dopamine D2 receptor (DRD2) genotype on neuroadaptive effects of alcohol and the clinical outeome of alcoholism. Pharmacogenetics 1997;7:271-81.CrossRefGoogle Scholar
George, DTLindquist, TRawlings, RREckhardt, MJMoss, HMathis, C, et al.Pharmacologic maintenance of abstinence in patients with alcoholism. Clin Pharmacol Ther 1992;52:553-60.CrossRefGoogle ScholarPubMed
George, DTRawlings, REckhardt, MJPhillips, MJShoaf, SLinnoila, M.Buspirone treatment of alcoholism: age of onset, and cerebrospinal fluid 5-hydroxyindoleacatic acid and homovanillic acid concentrations, but not medication treatment, predict return to drinking. Alcohol Clin Exp Res 1998;23:272-8.Google Scholar
Gianoulakis, CKrishnan, BThavundayil, J.Enhanced sensitivity of pituitary beta-endorphin to ethanol in subjects at high risk of alcoholism. Arch Gen Psychiatry 1996;53:250-7.CrossRefGoogle ScholarPubMed
Giros, BJaber, MJones, SRWightman, RMCaron, MG.Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transponer. Nature 1996;379:606-12.CrossRefGoogle Scholar
Grace, AA.Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia. Neurosci 1991;41:1-24.CrossRefGoogle ScholarPubMed
Heinz, ASchmidt, LGReischies, FM.Anhedonia in schizophrenic, depressed, or alcohol-dependent patients-neurobiological correlates. Phamacopsychiatry 1994;27(Suppl):7-10.CrossRefGoogle ScholarPubMed
Heinz, ADettling, MKuhn, SGraef, KJKuerten, IRommelspacher, H, et al.Blunted growth hormone response is associated with early relapse in alcohol-dependent patients. Alcohol Clin Exp Res 1995a;19:62-5.Google Scholar
Heinz, ALichrenberg-Kraaiz, BSällström Baum, SGräf, KKrüger, FDettling, M, et al.Evidence for prolonged recovery of dopaminergic transmission in alcoholics with poor treatment outcome. J Neural Transm 1995b;102:149-58.CrossRefGoogle Scholar
Heinz, ADufeu, PKuhn, SDettling, MGraef, KJKuerten, I, et al.Psychopathological and behavioral correlates of dopaminergic sensitivity in alcohol-dependent patients. Arch Gen Psychiatry 1996a;53:1123-8.CrossRefGoogle Scholar
Heinz, ASander, THarms, HFinckh, UKuhn, SDufeu, P, et al.Lack of allelic association of dopamine DI and D2 (TaqAl) receptor gene polymorphism with reduced dopaminergic sensitivity in alcoholism. Alcohol Clin Exp Res 1996b;20:1109-13.CrossRefGoogle Scholar
Heinz, ARagan, PJones, DWHommer, DWilliams, WKnable, MB, et al.Reduced serotonin transporters in alcoholism. AmJ Psychiatry 1998a;155:1544-9.CrossRefGoogle Scholar
Heinz, AKnable, MBCoppola, RGorey, JGJones, DWLee, KS, et al.Psychomotor slowing, negative symptoms and dopamine receptor availability-an IBZM study in neuroleptic-treated and drug-free schizophrenic patients. Schizophr Res 1998b;31:19-26.CrossRefGoogle Scholar
Heinz, ASaunders, RCKolachana, BSBertolino, AJones, DWGorey, JG, et al.Disinhibition of subcortical dopaminergic neurotransmission in rhesus monkeys with neonatal mesial temporal lesions. Synapse 1999;32:71-9.3.0.CO;2-Q>CrossRefGoogle Scholar
Heinz, AMann, KWeinberger, DRGoldman, D.Genetic and environmental effects on serotonin transporter availability and the response to alcohol intoxication. Alcohol Clin Exp Res 2001;25:487-95.CrossRefGoogle Scholar
Hietala, JWest, CSylälahti, ENygren, KLehikoinen, PSonninen, P, et al.Striatal dopamine receptor binding characteristics in vivo in patients with alcohol dependence. Psychopharmacology 1994;116:285-90.CrossRefGoogle ScholarPubMed
Hietala, JSyvalathi, EVilkman, HVuorio, KRakkolainen, VBergman, J, et al.Depressive symptoms and presynaptic dopamine function in neuroleptic-naive schizophrenia. Schizophr Res 1999;35:41-50.CrossRefGoogle ScholarPubMed
Higley, JDSuomi, SSLinnoila, M.A non-human primate model of type II excessive alcohol consumption. Parts 1 & 2. Alcohol Clin Exp Res 1996;20:629-51.CrossRefGoogle Scholar
Imperato, ADi Chiara, G.Preferential stimulation of dopamine release in the nucleus accumbens of freely moving rats by ethanol. J Pharmacol Exp Ther 1986;239:219-28.Google ScholarPubMed
Kalivas, PWStewart, J.Dopamine transmission in the initiation and expression of drug-and stress-induced sensitization of motor activity. Brain Res Rev 1991;16:223-44.CrossRefGoogle ScholarPubMed
Karlsson, PFarde, LHalldin, CSwahn, CGSedvall, G.Dopamine Dl-receptor binding in neuroleptic naive schizophrenic patients examined by PET. J Nucl Med 1999;40(Suppl):30P p.Google Scholar
Kegeles, LSZea-Ponce, YAbi-Dargham, ASchneider, Dvan Heertum, RMann, JJ, et al.Ketamine modulation of amphetamine-induced striatal dopamine release in humans measured by (1231) IBZM SPECT. J Nucl Med 1999;40:30P p.Google Scholar
Koob, GFLe Moal, M.Drug abuse: hedonic homeostatic dysregulation. Science 1997;278:52-8.CrossRefGoogle ScholarPubMed
Krystal, JHAbi-Dargham, ALaruelle, MMoghaddam, B.Pharmacological models of psychosis. In: Charney, DSNestler, EJBunney, BS, Eds. Neurobiology of mental illness. New York, Oxford: Oxford University Press; 1999 p. 214-24.Google Scholar
Laine, TPAhonen, ATorniainen, PHeikkilä, JPyhtinen, JRäsänen, P, et al.Dopamine transporters increase in human brain after alcohol withdrawal. Mol Psychiatry 1999;4:189-91.CrossRefGoogle ScholarPubMed
Laruelle, MIyer, RNAl-Tikriti, MSZea-Ponce, YMalison, RZoghbi, SS, et al.Microdialysis and SPECT measurements of amphetamine-induced dopamine release in non-human primates. Synapse 1996;25:1-14.3.0.CO;2-H>CrossRefGoogle Scholar
Le Marquand, DPhil, ROBenkelfat, C.Serotoninand alcohol intake, abuse, and dependence: findings in animal studies. Biol Psychiatry 1994;36:395-421.CrossRefGoogle Scholar
Lipska, BKJaskiw, GEWeinberger, DR.Postpubertal emergence of hyperresponsiveness to stress and to amphetamine after neonatal excitotoxic damage: a potential animal model of schizophrenia. Neuropsychopharmacology 1993;9:67-75.CrossRefGoogle ScholarPubMed
Lubow, REGewirtz, JC.Latent inhibition in humans: data, theory, and implications for schizophrenia. Psychol Bull 1995;117:87-103.CrossRefGoogle Scholar
Mattay, VSBerman, KFOstrem, JLEsposito, GVan Horn, JDBigelow, LB, et al.Dextroamphetamine enhance neural network-specific physiological signals: a positron-emission tomography rCBF study. J Neurosci 1996;16:4816-22.CrossRefGoogle ScholarPubMed
Mereu, GFadda, FGessa, GL.Ethanol stimulates the firing rate of nigral neurons in unanesthetized rats. Brain Res 1984;292:63-9.CrossRefGoogle ScholarPubMed
O’Connell, PWoodruff, PWRWright, IJones, PMurray, RM.Developmental insanity or dementia praecox: was the wrong concept adopted? Schizophr Res 1997;23:97-106.CrossRefGoogle ScholarPubMed
O’Donnell, PGreene, JPabello, NLewis, BLGrace, AA.Modulation of cell firing in the nucleus accumbens. Ann New York Acad Scie 1999;877:157-75.CrossRefGoogle ScholarPubMed
Okubo, YSuhara, TSuzuki, KKobayashi, KInoue, OTerasaki, O, et al.Decreased prefrontal dopamine DI receptors in schizophrenia revealed by PET. Nature 1997;385:634-6.CrossRefGoogle Scholar
Riederer, PSofic, ERausch, WDHebenstreit, GBriunvels, J.Pathobiochemistry of the extrapyramidal system: a “short note” review. In: Przuntek, HRiederer, P, Eds. Early diagnosis and preventive therapy in Parkinson’s diesease. Key topics in brain research. Vienna, Berlin, New York: Springer; 1989. p. 139-50.CrossRefGoogle Scholar
Robbins, TWEveritt, BJ.Neurobehavioral mechanisms of reward and motivation. Curt Opin Neurobiol 1996;6:228-36.CrossRefGoogle Scholar
Robinson, TEBerridge, KC.The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Rev 1993;18:247-91.CrossRefGoogle Scholar
Rommelspacher, HRaeder, CKaulen, PBrüning, G.Adaptive changes of dopamine-D2 receptors in rat brain following ethanol withdrawal: a quantitative autoradiographic investigation. Alcohol 1992;9:1-8.CrossRefGoogle ScholarPubMed
Rossetti, ZLMelis, FCarboni, SDiana, MGessa, GL.Alcohol withdrawal in rats is associated with a marked fall in extraneural dopamine. Alcohol Clin Exp Res 1992;16:529-32.CrossRefGoogle Scholar
Saunders, RCKolachana, BSBachevalier, JWeinberger, DR.Neonatal lesions of the medial temporal lobe disrupt prefrontal cortical regulation of striatal dopamine. Nature 1997;393:169-71.CrossRefGoogle Scholar
Schmidt, KNolte-Zenker, BPatzer, JBauer, MSchmidt, LGRommelspacher, H, et al.Psychopathological correlates of reduced dopamine receptor sensitivity in alcoholism and major depression. Pharmacopsychiatry 2001;34:66-72.CrossRefGoogle Scholar
Schultz, WApicella, PLjungberg, T.Responses of monkey dopamine neurons to reward and conditioned stimuli during successive steps of learning a delayed response task. J Neurosci 1993;13:900-13.CrossRefGoogle ScholarPubMed
Schultz, WDayan, PMontague, PR.A neural substrate of prediction and reward. Science 1997;275:1593-9.CrossRefGoogle ScholarPubMed
Schultz, WTremblay, LHollerman, JR.Reward prediction in primate basal ganglia and frontal cortex. Neuropharmacology 1998;37:421-9.CrossRefGoogle ScholarPubMed
Spanagel, RHerz, ASchippenberg, TS.Opposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. Proc Nati Acad Sci USA 1992;89:2046-50.CrossRefGoogle ScholarPubMed
Taber, MTDas, SFibiger, FIC.Cortical regulation of dopamine release: mediation via the ventral tegmental area. J Neurochem 1995;65:1407-10.CrossRefGoogle ScholarPubMed
Tiihonen, JKuikka, JBergström, KHakola, PKarhu, JRyynänen, OP, et al.Altered striatal dopamine re-uptake stites in habitually violent and non-violent alcoholics. Nat Med 1995;1:654-7.CrossRefGoogle Scholar
Tiihonen, JVilkman, H, Räsönen, P, Ryynänen, OPHakko, HBergman, J, et al.Striatal presynaptic dopamine function in type I alcoholics measured with positron emission tomography. Mol Psychiatry 1998;4:156-61.CrossRefGoogle Scholar
Tsai, GGastfriend, DRCoyle, JT.The glutamatergic basis of human alcoholism. Am J Psychiatry 1995;152:332-40.Google ScholarPubMed
Ungless, MAWhistler, JLMalenka, RCBonci, A.Singlecocaine exposure in vivo induces long-term potentiation in dopamine neurons. Nature 2001;411:583-7.CrossRefGoogle ScholarPubMed
Volkow, NDWang, GJFowler, JSlogan, JHitzemann, RDing, YS, et al.Decreases in dopamine receptors but not in dopamine transporters in alcoholics. Alcohol Clin Exp Res 1996;20:1594-8.CrossRefGoogle Scholar
Vorel, SRLiu, XHayes, RJSpector, JAGardner, EL.Relapse to cocaine-seeking after hippocampal thetaburst stimulation. Science 2001;292:1175-8.CrossRefGoogle Scholar
Watanabe, M.Reward expectancy in primate prefrontal neurons. Nature 1996;382:629-32.CrossRefGoogle ScholarPubMed
Weinberger, DR.Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry 1987;44:660-9.CrossRefGoogle ScholarPubMed
Weinberger, DRBerman, KFSuddath, RFuller Torrey, E.Evidence of dysfunction of prefrontal-limbic network in schizophrenia: a magnetic resonance imaging and regional cerebral blood flow study of discordant monozygotic twins. Am J Psychiatry 1992;149:890-7.Google ScholarPubMed
Williams, GVGoldman-Rakic, PS.Modulation of memory fields by dopamine DI receptors in prefrontal cortex. Nature 1995;376:572-5.CrossRefGoogle Scholar
Wise, RA.Neuroleptics and operant behavior: the anhedonia hypothesis. Behav Braein Sci 1982;5:39-87.CrossRefGoogle Scholar
Wise, RA.The neurobiology of craving: implications for the understanding of addiction. J Abnorm Psychol 1988;97:118-32.CrossRefGoogle Scholar
Wolf, SSJones, DWKnable, MBGorey, JGLee, KSHyde, TS, et al.Tourette syndrome: prediction of phenotypic variation in monozygotic twins by caudate nucleus D2 receptor binding. Science 1996;273:1225-7.CrossRefGoogle ScholarPubMed
Wong, DF, Wagner FIN Jr, Tune, LEDannals, RFPearlson, GDLinks, JM, et al.Positron emission tomography reveals elevated D-2 dopamine receptors in drug-naive schizophrenics. Science 1986;234:1558-63.CrossRefGoogle Scholar