Hostname: page-component-78c5997874-m6dg7 Total loading time: 0 Render date: 2024-11-19T23:11:37.828Z Has data issue: false hasContentIssue false

Dopaminergic dysfunction in alcoholism and schizophrenia – psychopathological and behavioral correlates

Published online by Cambridge University Press:  16 April 2020

A. Heinz*
Affiliation:
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, J5, 68159Mannheim, Germany
*
*Correspondence and reprints. E-mail address: [email protected] (A. Heinz).
Get access

Summary

Dysfunction of central dopaminergic neurotransmission has been implicated in the pathogenesis of schizophrenia as well as drug and alcohol dependence. Different drugs of abuse stimulate dopamine release in the ventral striatum and thus reinforce drug consumption. Increased subcortical dopamine release has also been associated with the pathogenesis of positive symptoms in schizophrenia and may be driven by a prefrontal dopaminergic dysfunction. These seemingly heterogeneous findings may be explained by recent research in non-human primates. According to these studies, reward anticipation but not anticipated reward consumption is accompanied by a phasic dopamine release in the striatum and prefrontal cortex. In the striatum, phasic dopamine release primarily affects motivation, psychomotor activation and reward craving, while in the prefrontal cortex, dopaminergic stimulation is involved in the activation of working memory and reward anticipation. In alcoholism, previously neutral stimuli that have been associated with alcohol intake can become conditioned cues which activate phasic dopamine release and reward craving. In schizophrenia, stress-induced or chaotic activation of dopamine release may attribute incentive salience to otherwise irrelevant stimuli and thus be involved in the pathogenesis of delusional mood and other positive symptoms. Studies in humans and non-human primates emphasize the role of dopaminergic neurotransmission in reward anticipation and its dysfunction in different neuropsychiatric diseases.

Type
Original article
Copyright
Copyright © Éditions scientifiques et médicales Elsevier SAS. 2002

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

Abercrombie, EDKeefe, KADiFrischia, DSZigmond, MJDifferential 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, Jet 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, GNeuroendocrine evidence for reduced dopamine receptor sensitivity in alcoholism. Alcohol Clin Exp Res 1992; 16; 71–4.CrossRefGoogle ScholarPubMed
Berridge, KCRobinson, TEWhat 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, GLA synaptic model of memory: long-term potentiation in the hippocampus. Nature 1993; 361; 31–9.CrossRefGoogle ScholarPubMed
Breier, ASu, TPSaunders, RCarson, REKolachana, BSde Bartolomeis, Aet al. Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. Proc Natl Acad Sci U S A 1997; 94; 2569–74.CrossRefGoogle ScholarPubMed
Breier, AAdler, CMWeisenfeld, NSu, TPElman, IPicken, Let 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, GDifferential inhibitory effects of a 5-HT3 antagonist on drug-induced stimulation of dopamine release. Eur J Pharmacol 1989 ; 164 : 515.CrossRefGoogle ScholarPubMed
Carlsson, AThe current status of the dopamine hypothesis of schizophrenia. Neuropsychopharmacology 1988; 1; 179–86.CrossRefGoogle ScholarPubMed
Chiamulera, CEpping-Jordan, MPZocchi, AMarcon, CCottiny, CTacconi, Set al. Reinforcing and locomotor stimulant effects of cocaine are absent in mGluR5 null mutant mice. Nat Neurosci 2001; 4; 873–4.CrossRefGoogle ScholarPubMed
Conrad, CDie beginnende Schizophreni.e, Stuttgart, New York: Thieme; 1992.Google Scholar
Cowen, MSLawrence, AJThe 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, Cet al. Presynaptic dopaminergic function in the striatum of schizophrenic patients. Schizophr Res 1997; 23; 167–74.CrossRefGoogle ScholarPubMed
Desimone, RIs dopamine a missing link?. Nature 1995; 376; 549–50.CrossRefGoogle ScholarPubMed
Dettling, MHeinz, ADufeu, PRommelspacher, HGräf, KJSchmidt, LGDopaminergic responsivity in alcoholism: trait-, state- or residual marker?. Am J Psychiat 1995; 152; 1317–21.Google ScholarPubMed
Di Chiara, GThe role of dopamine in drug abuse viewed from the perspective of its role in motivation. Drug Alc Dependence 1995; 38; 95–137.CrossRefGoogle ScholarPubMed
Farde, LWiesel, FAHall, HHalldin, CStone-Elander, SSedvall, GNo D-2 receptor increase in PET study of schizophrenia. Arch Gen Psychiatry 1987; 44; 671–2.CrossRefGoogle Scholar
Finckh, URommelspacher, HKuhn, SDufeu, POtto, GHeinz, Aet al. Influence of the dopamine D2 receptor (DRD2) genotype on neuroadaptive effects of alcohol and the clinical outcome of alcoholism. Pharmacogenetics 1997; 7; 271–81.CrossRefGoogle ScholarPubMed
George, DTLindquist, TRawlings, RREckhardt, MJMoss, HMathis, Cet al. Pharmacologic maintenance of abstinence in patients with alcoholism. Clin Pharmacol Ther 1992; 52; 553–60.CrossRefGoogle ScholarPubMed
George, DTRawlings, REckhardt, MJPhillips, MJShoaf, SLinnoila, MBuspirone 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, JEnhanced 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, MGHyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter. Nature 1996; 379; 606–12.CrossRefGoogle ScholarPubMed
Grace, AAPhasic 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, FMAnhedonia in schizophrenic, depressed, or alcohol-dependent patients – neurobiological correlates. Pharmacopsychiatry 1994 ; 27 (Suppl) : 7–10.CrossRefGoogle ScholarPubMed
Heinz, ADettling, MKuhn, SGraef, KJKuerten, IRommelspacher, Het al. Blunted growth hormone response is associated with early relapse in alcohol-dependent patients. Alcohol Clin Exp Res 1995; 19; 62–5.Google ScholarPubMed
Heinz, ALichtenberg-Kraag, BSällström Baum, SGräf, KKrüger, FDettling, Met al. Evidence for prolonged recovery of dopaminergic transmission in alcoholics with poor treatment outcome. J Neural Transm 1995; 102; 149–58.CrossRefGoogle ScholarPubMed
Heinz, ADufeu, PKuhn, SDettling, MGraef, KJKuerten, Iet al. Psychopathological and behavioral correlates of dopaminergic sensitivity in alcohol-dependent patients. Arch Gen Psychiatry 1996; 53; 1123–8.CrossRefGoogle ScholarPubMed
Heinz, ASander, THarms, HFinckh, UKuhn, SDufeu, Pet al. Lack of allelic association of dopamine D1 and D2 (TaqA1) receptor gene polymorphism with reduced dopaminergic sensitivity in alcoholism. Alcohol Clin Exp Res 1996; 20; 1109–13.CrossRefGoogle Scholar
Heinz, ARagan, PJones, DWHommer, DWilliams, WKnable, MBet al. Reduced serotonin transporters in alcoholism. Am J Psychiatry 1998; 155; 1544–9.CrossRefGoogle ScholarPubMed
Heinz, AKnable, MBCoppola, RGorey, JGJones, DWLee, KSet al. Psychomotor slowing, negative symptoms and dopamine receptor availability – an IBZM study in neuroleptic-treated and drug-free schizophrenic patients. Schizophr Res 1998; 31; 19–26.CrossRefGoogle ScholarPubMed
Heinz, ASaunders, RCKolachana, BSBertolino, AJones, DWGorey, JGet 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, DGenetic 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, CSylvälahti, ENygren, KLehikoinen, PSonninen, Pet 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, Jet al. Depressive symptoms and presynaptic dopamine function in neuroleptic-naive schizophrenia. Schizophr Res 1999; 35; 41–50.CrossRefGoogle ScholarPubMed
Higley, JDSuomi, SSLinnoila, MA 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, GPreferential 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, JDopamine 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, GDopamine D1-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, JJet al. Ketamine modulation of amphetamine-induced striatal dopamine release in humans measured by (123I)IBZM SPECT. J Nucl Med 1999 ; 40 : 30P p.Google Scholar
Koob, GFLe Moal, MDrug abuse: hedonic homeostatic dysregulation. Science 1997; 278; 52–8.CrossRefGoogle ScholarPubMed
Krystal, JHAbi-Dargham, ALaruelle, MMoghaddam, BPharmacological 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, Pet 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, SSet 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, CSerotoninand alcohol intake, abuse, and dependence: findings in animal studies. Biol Psychiatry 1994; 36; 395–421.CrossRefGoogle Scholar
Lipska, BKJaskiw, GEWeinberger, DRPostpubertal 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, JCLatent inhibition in humans: data, theory, and implications for schizophrenia. Psychol Bull 1995; 117; 87–103.CrossRefGoogle Scholar
Mattay, VSBerman, KFOstrem, JLEsposito, GVan Horn, JDBigelow, LBet 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, GLEthanol stimulates the firing rate of nigral neurons in unanesthetized rats. Brain Res 1984; 292; 63–9.CrossRefGoogle ScholarPubMed
O’Connell, PWoodruff, PWRWright, IJones, PMurray, RMDevelopmental insanity or dementia praecox: was the wrong concept adopted?. Schizophr Res 1997; 23; 97–106.CrossRefGoogle ScholarPubMed
O’Donnell, PGreene, JPabello, NLewis, BLGrace, AAModulation of cell firing in the nucleus accumbens. Ann New York Acad Scie 1999; 877; 157–75.CrossRefGoogle ScholarPubMed
Okubo, YSuhara, TSuzuki, KKobayashi, KInoue, OTerasaki, Oet al. Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET. Nature 1997; 385; 634–6.CrossRefGoogle ScholarPubMed
Riederer, PSofic, ERausch, WDHebenstreit, GBriunvels, JPathobiochemistry of the extrapyramidal system: a “short note” review. In: Przuntek, HRiederer, PEarly 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, BJNeurobehavioral mechanisms of reward and motivation. Curr Opin Neurobiol 1996; 6; 228–36.CrossRefGoogle Scholar
Robinson, TEBerridge, KCThe neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Rev 1993; 18; 247–91.CrossRefGoogle Scholar
Rommelspacher, HRaeder, CKaulen, PBrüning, GAdaptive 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, GLAlcohol 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, DRNeonatal 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, Het al. Psychopathological correlates of reduced dopamine receptor sensitivity in alcoholism and major depression. Pharmacopsychiatry 2001; 34; 66–72.CrossRefGoogle Scholar
Schultz, WApicella, PLjungberg, TResponses 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, PRA neural substrate of prediction and reward. Science 1997; 275; 1593–9.CrossRefGoogle ScholarPubMed
Schultz, WTremblay, LHollerman, JRReward prediction in primate basal ganglia and frontal cortex. Neuropharmacology 1998; 37; 421–9.CrossRefGoogle ScholarPubMed
Spanagel, RHerz, ASchippenberg, TSOpposing tonically active endogenous opioid systems modulate the mesolimbic dopaminergic pathway. Proc Natl Acad Sci U S A 1992; 89; 2046–50.CrossRefGoogle ScholarPubMed
Taber, MTDas, SFibiger, HCCortical regulation of dopamine release: mediation via the ventral tegmental area. J Neurochem 1995; 65; 1407–10.CrossRefGoogle ScholarPubMed
Tiihonen, JKuikka, JBergström, KHakola, PKarhu, JRyynänen, OPet al. Altered striatal dopamine re-uptake stites in habitually violent and non-violent alcoholics. Nat M 1995; 1; 654–7.CrossRefGoogle Scholar
Tiihonen, JVilkman, HRäsönen, PRyynänen, OPHakko, HBergman, Jet al. Striatal presynaptic dopamine function in type 1 alcoholics measured with positron emission tomography. Mol Psychiatry 1998; 4; 156–61.CrossRefGoogle Scholar
Tsai, GGastfriend, DRCoyle, JTThe glutamatergic basis of human alcoholism. Am J Psychiatry 1995; 152; 332–40.Google ScholarPubMed
Ungless, MAWhistler, JLMalenka, RCBonci, ASingle cocaine exposure in vivo induces long-term potentiation in dopamine neurons. Nature 2001; 411; 583–7.CrossRefGoogle ScholarPubMed
Volkow, NDWang, GJFowler, JSLogan, JHitzemann, RDing, YSet 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, ELRelapse to cocaine-seeking after hippocampal theta-burst stimulation. Science 2001; 292; 1175–8.CrossRefGoogle ScholarPubMed
Watanabe, MReward expectancy in primate prefrontal neurons. Nature 1996; 382; 629–32.CrossRefGoogle ScholarPubMed
Weinberger, DRImplications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry 1987; 44; 660–9.CrossRefGoogle ScholarPubMed
Weinberger, DRBerman, KFSuddath, RFuller Torrey, EEvidence 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, PSModulation of memory fields by dopamine D1 receptors in prefrontal cortex. Nature 1995; 376; 572–5.CrossRefGoogle ScholarPubMed
Wise, RANeuroleptics and operant behavior: the anhedonia hypothesis. Behav Brain Sci 1982; 5; 39–87.CrossRefGoogle Scholar
Wise, RAThe neurobiology of craving: implications for the understanding of addiction. J Abnorm Psychol 1988; 97; 118–32.CrossRefGoogle Scholar
Wolf, SSJones, DWKnable, MBGorey, JGLee, KSHyde, TSet al. Tourette syndrome: prediction of phenotypic variation in monozygotic twins by caudate nucleus D2 receptor binding. Science 1996; 273; 1225–7.CrossRefGoogle ScholarPubMed
Wong, DFWagner, JrTune, HNDannals, RFPearlson, GDLinks, JMet al. Positron emission tomography reveals elevated D-2 dopamine receptors in drug-naive schizophrenics. Science 1986; 234; 1558–63.CrossRefGoogle Scholar
Submit a response

Comments

No Comments have been published for this article.