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Mecanismos de acción de los medicamentos antipsicóticos de segunda generación en la esquizofrenia: conocimientos obtenidos a partir de los estudios de imágenes cerebrales

Published online by Cambridge University Press:  12 May 2020

Anissa Abi-Dargham  and
Marc Laruelle
Anissa Abi-Dargham
Affiliation:
Departamentos de Psiquiatría y Radiología, Instituto Psiquiátrico del Estado de Nueva Cork, Unidad 31, Columbio University College of Physicians and Surgeons, 1051 Riverside Drive, Nueva York, N Y 10032, EE.UU.
Marc Laruelle
Affiliation:
Departamentos de Psiquiatría y Radiología, Instituto Psiquiátrico del Estado de Nueva Cork, Unidad 31, Columbio University College of Physicians and Surgeons, 1051 Riverside Drive, Nueva York, N Y 10032, EE.UU.
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Resumen

Múltiples líneas de datos, incluidos estudios de imágenes recientes, indican que la esquizofrenia se asocia con un desequilibrio del sistema dopaminérgico que implica la hiperestimulación de los receptores D2 de dopamina (DA) estriatales y la infraestimulación de los receptores D1 de DA corticales. Presumiblemente, este endofenotipo de la DA surge del trasfondo de una disconectividad sináptica más general, que implica alteraciones en las funciones del IV-metil-D-aspartato (NMDA) y glutamatérgica (GLU). Igualmente importante es el hecho de que esta disregulación de la DA podría deteriorar más la transmisión del NMDA. Los medicamentos antipsicóticos de primera generación (APG) se caracterizan por elevada afinidad con los receptores D2 y, por lo general, su alta ocupación. La eficacia de los APG está limitada por una elevada incidencia de efectos secundarios extrapiramidades (ESEP). Los medicamentos antipsicóticos de segunda generación (ASG) muestran una reducción de la tendencia a los ESEP y un aumento modesto pero clínicamente significativo de la eficacia terapéutica. Comparado con los APG, la mejora de la acción terapéutica de los ASG deriva probablemente de un bloqueo más moderado del receptor D2. Revisaremos los efectos de los ASG sobre otros sistemas neurotransmisores y concluiremos haciendo resaltar la importancia de las estrategias terapéuticas dirigidas a aumentar directamente la transmisión del receptor D1 de DA prefrontal o la transmisión del NMDA para aumentar el efecto terapéutico del antagonismo moderado del receptor D2.

Keywords

Medicamentos antipsicóticosDopaminaGlutamatoEsquizofreniaTEPSPECT
Type
Artículo original
Information
European Psychiatry (Ed. Española) , Volume 12 , Issue 4 , May 2005 , pp. 231 - 244
Copyright
Copyright © European Psychiatric Association 2005

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Footnotes

Abi-Dargham A, Laruelle M. Mechanisms of action of second generation antipsychotic drugs in schizophrenia; insights from brain imaging studies. Eur Psychiatry 2005;20:15-27.

References

Bibliografía

[1]Abi-Dargham, AGil, RKrystal, JBaldwin, RMSeibyl, JPBowers, M, et al. Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort. Am J Psychiatry 1998; 155: 761-7.Google Scholar
[2]Abi-Dargham, ARodenhiser, JPrintz, DZea-Ponce, YGil, RKegeles, L, et al. Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. Proc Natl Acad Sci USA 2000; 97: 8104-9.CrossRefGoogle Scholar
[3]Abi-Dargham, AMawlawi, OLombardo, IGil, R, Martinez D Huang Y, et al. Prefrontal dopamine D, receptors and working memory in schizophrenia. J Neurosci 2002; 22: 3708-19.CrossRefGoogle Scholar
[4]Ahlenius, S. Clozapine: dopamine D1 receptor agonism in the prefrontal cortex as the code to decipher a Rosetta stone of antipsychotic drugs. Pharmacol Toxicol 1999; 84: 193-6.CrossRefGoogle ScholarPubMed
[5]Akil, MPierri, JNWhitehead, REEdgar, CLMohila, CSampson, AR, et al. Lamina-specific alterations in the dopamine innervation of the prefrontal cortex in schizophrenic subjects. Am J Psychiatry 1999; 156: 1580-9.CrossRefGoogle ScholarPubMed
[6]Anden, NE. Dopamine turnover in the Corpus striatum and the lumbic system after treatment with neuroleptic and anti-acotylcholine drugs. J Pharm Pharmacol 1972; 24: 905-6.CrossRefGoogle ScholarPubMed
[7]Anden, NStock, G. Effect of clozapine on the turnover of dopamine in the Corpus striatum and in the limbic system. J Pharm Pharmacol 1973; 25: 346-8.CrossRefGoogle ScholarPubMed
[8]Angrist, BVan Kammen, DP. CNS stimulants as a tool in the study of schizophrenia. Trends Neurosci 1984; 7: 388-90.CrossRefGoogle Scholar
[9]Arnt, JSkarsfeldt, T. Do novel antipsychotics have similar pharmacological characteristics? A review of the evidence. Neuropsychopharmacology 1998; 18: 63–101.CrossRefGoogle Scholar
[10]Baldessarini, RJFrankenburg, FR. Clozapine. A novel antipsychotic agent. N Engl J Med 1991; 324: 746-54.Google ScholarPubMed
[11]Bertolino, ABreier, ACallicott, JHAdler, CMattay, VSShapiro, M, et al. The relationship between dorsolateral prefrontal neuronal Nacetylaspartate and evoked ralease of striatal dopamine in schizophrenia. Neuropsychopharmacology 2000; 22: 125-32.CrossRefGoogle Scholar
[12]Bigliani, VMulligan, RSActon, PD. Visvikis, DEll, PJStephenson, C, et al. In vivo occupancy of striatal and temporal cortical D2/D3 dopamine receptors by typical antipsychotic drugs. [123]epidepride single photon emission tomography (SPET) study. Br J Psychiatry 1999; 175: 231-8.Google Scholar
[13]Bigliani, VMulligan, RSActon, PDOhlsen, RIPike, VWEll, PJ, et al. Striatal and temporal cortical D2/D3 receptor occupancy by olanzapine and sertindole in vivo: a [123]epidepride single photon emission tomography (SPET) study. Psychopharmacology (Berlin) 2000; 150: 132-40.CrossRefGoogle Scholar
[14]Breier, ASu, TPSaunders, RCarson, REKolachana, BSDebartolomeis, A, et al. Schizophrenia is associated with elevated amphetamine induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. Proc Nati Acad Sci USA 1997; 94: 2569-74.CrossRefGoogle ScholarPubMed
[15]Bressan, RAErlandsson, KJones, HMMulligan, RSEli, PJPilowsky, LS. Optimizing limbic selective D2/D3 receptor occupancy by risperidone: a [123I]epidepride SPET study. J Clin Psychopharmacol 2003; 23: 5–14.CrossRefGoogle Scholar
[16]Bressan, RAErlandsson, KJones, HMMulligan, RFlanagan, RJEli, N, et al. Is regionally selective D2/D3 dopamine occupancy sufficient for atypical antipsychotic effect? An in vivo quantitative [123I]epidepride SPET study of amisulpride-treated patients. Am J Psychiatry 2003; 160: 1413-20.CrossRefGoogle ScholarPubMed
[17]Carlsson, ALindqvist, M. Effect of chlorpromazine or haloperidol on formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta Pharmacol Toxicol (Copenh) 1963; 20: 140-4.CrossRefGoogle ScholarPubMed
[18]Carpenter, WTBuchanan, RW. Schizophrenia. N Engl J Med 1994; 330: 681-90.CrossRefGoogle ScholarPubMed
[19]Centonze, DPicconi, BGubellini, PBernardi, GCalabresi, R. Dopaminergic control of synaptic plasticity in the dorsal striatum. Eur J Neurosci 2001; 13: 1071-7.CrossRefGoogle ScholarPubMed
[20]Cepeda, CLevine, MS. Dopamine and A-methyl-D-aspartate receptor interactions in the neostriatum. Dev Neurosci 1998; 20: 1–8.CrossRefGoogle ScholarPubMed
[21]Cepeda, CHurst, RSAltemus, KLFlores-Hernandez, JCalvert, CRJokel, ES, et al. Facilitated glutamatergic transmission in the striatum of D2 dopamine receptor-deficient mice. J Neurophysiol 2001; 85: 659-70.CrossRefGoogle ScholarPubMed
[22]Chiodo, LBunney, B. Typical and atypical neuroleptics: differential effects of chronic administration on the activity of A9 and A10 midbrain dopaminergic neurons. J Neurosci 1983; 3: 1607-9.CrossRefGoogle ScholarPubMed
[23]Creese, IBurt, DRSnyder, SH. Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 1976; 19: 481-3.CrossRefGoogle Scholar
[24]Cussac, DPasteau, VMillan, MJ. Characterisation of Gs activation by dopamine D1receptors using an antibody capture assay: antagonist properties of clozapine. Eur J Pharmacol 2004; 485: 111-7.CrossRefGoogle ScholarPubMed
[25]Daniel, DGWeinberger, DRJones, DWZigun, JRCoppola, RHandel, S, et al. The effect of amphetamine on regional cerebral blood flow during cognitive activation in schizophrenia. J Neurosci 1991; 11: 1907-17.CrossRefGoogle Scholar
[26]Dao-Castellana, MHPaillere-Martinot, MLHantraye, PAttar-Levy, DRemy, PCrouzel, C, et al. Presynaptic dopaminergic function in the striatum of schizophrenic patients. Schizophr Res 1997; 23: 167- 74.CrossRefGoogle ScholarPubMed
[27]Davis, KLKahn, RSKo, GDavidson, M. Dopamine in schizophrenia: a review and reconceptualization. Am J Psychiatry 1991; 148: 1474-86.Google ScholarPubMed
[28]Davis, JMChen, NGlick, ID. A meta-analysis of the efficacy of secondgeneration antipsychotics. Arch Gen Psychiatry 2003; 60: 553-64.CrossRefGoogle Scholar
[29]de Beaurepaire, RLabelle, ANaber, DJones, BDBarnes, TR. An upen trial of the D1 antagonist SCH 39166 in six cases of acute psychotic States. Psychopharmacology (Berlin) 1995; 121: 323-7.CrossRefGoogle Scholar
[30]de Paulis, T. M-100907 (Aventis). Curr Opin Invest Drugs 2001; 2: 123-32.Google Scholar
[31]Dean, BScarr, E. Antipsychotic drugs: evolving mechanisms of action with improved therapeutic benefits. Curr Drug Targets CNS Neurol Disord 2004; 3: 217–2175.CrossRefGoogle ScholarPubMed
[32]Delay, JDeniker, PHarl, JM. Therapeutic use in psychiatry of phenothiazine of central elective action (4560 RP). Ann Med Psychol (Paris) 1952: 112-7.Google Scholar
[33]DeLeon, APatel, NCCrismon, ML. Aripiprazole: a comprehensive review of its pharmacology, clinical etficacy, and tolerability. Clin Ther 2004; 26: 649-56.CrossRefGoogle ScholarPubMed
[34]Den Boer, JAVan Megen, HJFleischhacker, WWLouwerens, JWSlaap, BRWestenberg, HG, et al. Differential effects of the D,-DA receptor antagonist SCH39166 on positive and negative symptoms of schizophrenia. Psychopharmacology (Berlin) 1995; 121: 317-22.CrossRefGoogle Scholar
[35]Deutch, AYClark, WARoth, RH. Prefrontal cortical dopamine depletion enhances the responsiveness of mesolimbic dopamine neurons to stress. Brain Res 1990; 521: 311-5.CrossRefGoogle ScholarPubMed
[36]Deutch, AYMoghadam, BInnis, RKrystal, JAghajanian, GBunney, B, et al. Mechanisms of action of atypical antipsychotic drugs. Implication for novel therapeutic strategies for schizophrenia. Schizophr Res 1991; 4: 21–56.Google ScholarPubMed
[37]Deutch, AYLee, MCIadarola, MJ. Regionally specific effects of atypical antipsychotic drugs on striatal fos expression: the nucleus accumbens shell as a locus of antipsychotic action. Mol Cell Neurosci 1992; 3: 332-41.CrossRefGoogle ScholarPubMed
[38]Dolan, RJFletcher, PFrith, CDFriston, KJFrackowiak, RSGrasby, PM. Dopaminergic modulation of impaired cognitive activation in the antenor cingulate cortex in schizophrenia. Nature 1995; 378: 180-2.CrossRefGoogle Scholar
[39]Dunah, AWStandaert, DG. Dopamine D1 receptor-dependent trafficking of striatal NMDA glutamate receptors to the postsynaptic membrane. J Neurosci 2001; 21: 5546-8.CrossRefGoogle ScholarPubMed
[40]Duncan, GEZorn, SLieberman, JA. Mechanisms of typical and atypical antipsychotic drug action in relation to dopamine and NMDA receptor hypofunction hypotheses of schizophrenia. Mol Psychiatry 1999; 4: 418-28.CrossRefGoogle ScholarPubMed
[41]Farde, LWiesel, FAHalldin, CSedvall, G. Central D2-dopamine receptor occupancy in schizophrenic patients treated with antipsychotic drugs. Arch Gen Psychiatry 1988; 45: 71-6.CrossRefGoogle ScholarPubMed
[42]Farde, LNordström, ALWiesel, FAPauli, SHalldin, CSedvall, G. Positron emission tomography analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Arch Gen Psychiatry 1992; 49: 538-44.CrossRefGoogle ScholarPubMed
[43]Flores-Hernandez, JCepeda, CHernandez-Echeagaray, ECalvert, CRJokel, ESFienberg, AA, et al. Dopamine enhancement of NMDA currents in dissociated medium-sized striatal neurons: role of D1 receptors and DARPP-32. J Neurophysiol 2002; 88: 3010-20.CrossRefGoogle ScholarPubMed
[44]Frankle, WGLerma, JLaruelle, M. The synaptic hypothesis of schizophrenia. Neuron 2003; 39: 205-16.CrossRefGoogle ScholarPubMed
[45]Frankle, WGil, RHackett, EMawlawi, OZea-Ponce, YZhu, Z, et al. Occupancy of dopamine D2 receptors by the atypical antipsychotic drags risperidone and olanzapine: theoretical implications. Psychopharmacology (Berlin) 2004 In press.CrossRefGoogle Scholar
[46]Friedman, JITemporini, HDavis, KL. Pharmacologic strategies for augmenting cognitive performance in schizophrenia. Biol Psychiatry 1999; 45: 1–6.CrossRefGoogle Scholar
[47]Geddes, JFreemantle, NHarrison, PBebbington, P. Atypical antipsychotics in the treatment of schizophrenia: systematic OverView and meta-regression analysis. BMJ 2000; 321: 1371-6.CrossRefGoogle ScholarPubMed
[48]Gefvert, OBergstrom, MLangstrom, BLundberg, TLindstrom, LYates, R. Time course of central nervous dopamine-D-2 and 5-HT2 receptor blockade and plasma drag concentrations after discontinuation of quetiapine (Seroquel(R)) in patients with schizophrenia. Psychopharmacology (Berl) 1998; 135: 119-26.CrossRefGoogle Scholar
[49]Gessa, GLDevoto, PDiana, MFlore, GMelis, MPistis, M. Dissociation of haloperidol, clozapine, and olanzapine effects on electrical activity of mesocortical dopamine neurons and dopamine ralease in the prefrontal cortex. Neuropsychopharmacology 2000; 22: 642-9.CrossRefGoogle ScholarPubMed
[50]Goff, DCCoyle, JT. The emerging role of glutamate in the pathophysiology and treatment of schizophrenia. Am J Psychiatry 2001; 158: 1367-77.CrossRefGoogle ScholarPubMed
[51]Goff, DCTsai, GLevitt, JAmito, EManoach, DSchoenfeld, DA, et al. A placebo-controlled trial of D-cycloserine added to conventional neuroleptics in patients with schizophrenia. Arch Gen Psychiatry 1999; 56: 21-7.CrossRefGoogle ScholarPubMed
[52]Goldman-Rakic, PS, Muly 3rd EC, Williams GV. D(l) receptors in prefrontal cells and circuits. Brain Res Brain Res Rev 2000; 31: 295- 301.CrossRefGoogle Scholar
[53]Grate, AA. Phasic versus tonic dopamine ralease and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia. Neuroscience 1991; 41: 1–24.Google Scholar
[54]Grate, AABunney, BSMoore, HTodd, CL. Dopamine-cell depolarization block as a model for the therapeutic actions of antipsychotic drugs. Trends Neurosci 1997; 20: 31-7.Google Scholar
[55]Graybiel, AM. The basal ganglio and cognitive pattern generators. Schizophr Bull 1997; 23: 459-69.CrossRefGoogle Scholar
[56]Guo, NHwang, DLo, EHuang, YHLaruelle, MAbi-Dargham, A. Dopamine depletion and in vivo binding of PET D, radioligands: implication for imaging studies in schizophrenia. Neuropsychopharmacology 2003; 28: 1703-11.CrossRefGoogle Scholar
[57]Harrison, PJWeinberger, DR. Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence. Mol Psychiatry 2004 In press.CrossRefGoogle Scholar
[58]Heresco-Levy, U. Glutamatergic neurotransmission modulation and the mechanisms of antipsychotic atypicality. Prog Neuropsychopharmacol Biol Psychiatry 2003; 27: 1113-23.CrossRefGoogle ScholarPubMed
[59]Heresco-Levy, UJavitt, DCErmilov, MSilipo, GShimoni, J. Doubleblind, placebo-controlled, crossover trial of d-cycloserine adjuvant therapy for treatment-resistant schizophrenia. Int J Neuropsychopharmacol 1998; 1: 131-6.CrossRefGoogle Scholar
[60]Heresco-Levy, UJavitt, DCErmilov, MMordel, CSilipo, GLichtenstein, M. Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia. Arch Gen Psychiatry 1999; 56: 29–36.CrossRefGoogle ScholarPubMed
[61]Heresco-Levy, UErmilov, MShimoni, JShapira, BSilipo, GJavitt, DC. Placebo-controlled trial of d-cyclosenne added to conventional neuroleptics, olanzapine and rispendone in schizophrenia. Am J Psychiatry 2002; 159: 480-2.CrossRefGoogle Scholar
[62]Hernandez-Lopez, SBurgas, JSurmeier, DJReyes, AGalarraga, E. D1 receptor activation enhances evoked discharge in neostriatal medium spiny neurons by modulating an L-type Ca2+ conductance. J Neurosci 1997; 17: 3334-42.CrossRefGoogle ScholarPubMed
[63]Hietala, JSyvalahti, EVuorio, KRakkolainen, VBergman, JHaaparanta, M, et al. Presynaptic dopamine function in striatum of neuroleptic- naive schizophrenic patients. Lancet 1995; 346: 1130-1.CrossRefGoogle ScholarPubMed
[64]Hietala, JSyvalahti, 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
[65]Hippius, H. A historical perspective of clozapine. J Clin Psychiatry 1999; 60: S22-3.Google ScholarPubMed
[66]Ichikawa, JIshii, HBonaccorso, SFowler, WLO'Laughlin, IAMeltzer, HY. 5-HT(2A) and D(2) receptor blockade increases cortical DA ralease via 5-HT(IA) receptor activation: a possible mechanism of atypical antipsychotic-induced cortical dopamine ralease. J [88] Neurochem 2001; 76: 1521-31.CrossRefGoogle Scholar
[67]Ichikawa, JDai, JO'Laughlin, IAFowler, WLMeltzer, HY. Atypical, but not typical, antipsychotic drugs increase cortical acetylcholine ralease without an effect in the nucleus accumbens or striatum. Neuropsychopharmacology 2002; 26: 325-9.CrossRefGoogle ScholarPubMed
[68]Idanpaan-Heikkila, JAlhava, EOlkinuora, MPalva, IP. Agranulocytosis during treatment with clozapine. Eur J Clin Pharmacol 1977; 11: 193-8.CrossRefGoogle Scholar
[69]Jackson, DMWikstrom, HLiao, Y. Is clozapine an (partial) agonist at both dopamine D1 and D2 receptors? Psychopharmacology (Berlin) 1998; 138: 213-6.CrossRefGoogle ScholarPubMed
[70]Javitt, DCZukin, SR. Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry 1991; 148: 1301-8.Google ScholarPubMed
[71]Javitt, DCZylberman, IZukin, SRHeresco-Levy, ULindenmayer, JP. Amelioration of negative symptoms in schizophrenia by glycine. Am J Psychiatry 1994; 151: 1234-6.Google ScholarPubMed
[72]Javitt, DCSilipo, GCienfuegos, AShelley, AMBark, NPark, M, et al. Adjunctive high-dose glycine in the treatment of schizophrenia. Int J Neuropsychopharmacol 2001; 4: 385-91.CrossRefGoogle ScholarPubMed
[73]Jentsch, JDRoth, RH. The neuropsychopharmacology of phencyclidine: from NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia. Neuropsychopharmacology 1999; 20: 201-5.CrossRefGoogle ScholarPubMed
[74]Kahn, RSHarvey, PDDavidson, MKeefe, RSApter, SNeale, JM, et al. Neuropsychological correlates of central monoamine function in chronic schizophrenia: relationship between CSF metabolites and cognitive function. Schizophr Res 1994; 11: 217-24.CrossRefGoogle ScholarPubMed
[75]Kane, JHonigfold, GSinger, JMeltzer, HY. Clozapine for the treatment- resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry 1988; 45: 789-96.Google ScholarPubMed
[76]Kapur, S, Seeman R Antipsychotic agents differ in how fast they come off the dopamine D2 receptors. Implications for atypical antipsychotic action. J Psychiatry Neurosci 2000; 25: 161-6.Google ScholarPubMed
[77]Kapar, S, Seeman R Does fast dissociation from the dopamine d(2) [98] receptor explain the action of atypical antipsychotics? A new hypothesis. Am J Psychiatry 2001; 158: 360-9.CrossRefGoogle Scholar
[78]Kapur, SZipursky, RBRemington, GJones, CDaSilva, JWilson, AA, et al. 5-HT2 and D2 receptor occupancy of olanzapine in schizophrenia: a PET investigation. Am J Psychiatry 1998; 155: 921-8.Google Scholar
[79]Kapur, SZipursky, RBRemington, G. Clinical and theoretical implications of 5-HT2 and D2 receptor occupancy of clozapine, risperidone, and olanzapine in schizophrenia. Am J Psychiatry 1999; 156: 286-93.Google Scholar
[80]Kapur, SZipursky, RJones, CRemington, GHoule, S. Relationship between dopamine D(2) occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia. Am J Psychiatry 2000; 157: 514-20.CrossRefGoogle ScholarPubMed
[81]Karle, JClemmesen, LHansen, LAndersen, MAndersen, JFensbo, C, et al. NNC 01-0687, a selective dopamine D1 receptor antagonist, in the treatment of schizophrenia. Psychopharmacology (Berlin) 1995; 121: 328-9.CrossRefGoogle ScholarPubMed
[82]Karlsson, PSmith, LFarde, LHamryd, CSedvall, GWiesel, FA. Lack of apparent antipsychotic effect of the D1-dopamine receptor antagonist SCH39166 in acutely ill schizophrenic patients. Psychopharmacology (Berlin) 1995; 121: 309-16.CrossRefGoogle ScholarPubMed
[83]Karlsson, PFarde, LHalldin, CSedvall, G. PET study of D(l) dopamine receptor binding in neuroleptic-naive patients with schizophrenia. Am J Psychiatry 2002; 159: 761-7.CrossRefGoogle Scholar
[84]Knable, MBWeinberger, DR. Dopamine, the prefrontal cortex and schizophrenia. J Psychopharmacol 1997; 11: 123-31.CrossRefGoogle Scholar
[85]Kolachana, BSSaunders, RCBachevalier, JWeinberger, DR. Abnormal prefrontal cortical regulation of striatal dopamine ralease after neonatal medial temporal-limbic lesions in rhesus monkeys. Soc Neurosci 1996 Abst. 22:1974.Google Scholar
[86]Konradi, CHeckers, S. Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment. Pharmacol Ther 2003; 97: 153-79.CrossRefGoogle ScholarPubMed
[87]Kotter, R. Postsynaptic integration of glutamatergic and dopaminergic signais in the striatum. Prog Neurobiol 1994; 44: 163-96.CrossRefGoogle ScholarPubMed
[88]Krystal, JHKarper, LPSeibyl, JPFreeman, GKDelaney, RBremner, JD, et al. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotornimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry 1994; 51: 199–214.Google Scholar
[89]Kufferle, BTauscher, JAsenbaum, SVesely, CPodreka, IBrucke, T, et al. IBZM SPECT imaging of striatal dopamine-2 receptors in psychotic patients treated with the novel antipsychotic substance quetiapine in comparison to clozapine and haloperidol. Psychopharmacology (Berl) 1997; 133: 323-8.CrossRefGoogle ScholarPubMed
[90]Lahti, ACKoffel, BLaPorte, DTamminga, CA. Subanesthotic doses of ketamine stimulate psychosis in schizophrenia. Neuropsychopharmacology 1995; 13: 9–19.CrossRefGoogle ScholarPubMed
[91]Lahti, ACWeiler, MATamara Michaelidis, BAParwani, ATamminga, CA. Effects of ketamine in nommal and schizophrenic volunteers. Neuropsychopharmacology 2001; 25: 455-67.CrossRefGoogle ScholarPubMed
[92]Laruelle, M. Dopamine transmission in the schizophrenic brain. In: Weinberger, DRHirsch, S, editors. Schizophrenia, 2nd ed. Oxford, UK: Blackwell Publishing; 2003. p. 365-87.CrossRefGoogle Scholar
[93]Laruelle, MAbi-Dargham, AVan Dyck, CHGil, RDe Souza, CDErdos, J, et al. Single photon emission computerized tomography imaging of amphetamine-induced dopamine ralease in drug free schizophrenic subjects. Proc Nati Acad Sci USA 1996; 93: 9235-40.CrossRefGoogle ScholarPubMed
[94]Laruelle, MAbi-Dargham, AGil, RKegeles, LInnis, R. Increased dopamine transmission in schizophrenia: relationship to illness pitases. Biol Psychiatry 1999; 46: 56–72.CrossRefGoogle Scholar
[95]Leveque, JCMacias, WRajadhyaksha, ACarlson, RRBarczak, AKang, S, et al. Intracellular modulation of NMDA receptor function by antipsychotic drugs. J Neurosci 2000; 20: 4011-20.CrossRefGoogle ScholarPubMed
[96]Levine, MSLi, ZCepeda, CCromwell, HCAltemus, KL. Neuromodulatory actions of dopamine on synaptically-evoked neostriatal responses in slices. Synapse 1996; 24: 65–78.CrossRefGoogle ScholarPubMed
[97]Lidsky, TI. Reevaluation of the mesolimbic hypothesis of antipsychotic drug action. Schizophr Bull 1995; 21: 67–74.CrossRefGoogle ScholarPubMed
[98]Liebemman, JAKane, JMAlvir, J. Provocative tests with psychostimulant drugs in schizophrenia. Psychopharmacology (Berl) 1987; 91: 415-33.CrossRefGoogle Scholar
[99]Lindstrom, LHGefvert, OHagberg, GLundberg, TBergstrom, MHartvig, P, et al. Increased dopamine synthesis rate in medial prefrontal cortex and striatum in schizophrenia indicated by l-(beta-llC) DOPA and PET. Biol Psychiatry 1999; 46: 681-8.CrossRefGoogle Scholar
[100]Lindvall, OBjörklund, A. Dopamine- and norepinephrine-containing neuron Systems: their anatomy in the rat brain. In: Emson, P, editor. Chemical neuroanatomy. New York: Raven Press; 1983. p. 229-55.Google Scholar
[101]Mamo, DKapur, SShammi, CMPapatheodorou, GMann, SThernen, F, et al. A PET study of dopamine D2 and serotonin 5-HT2 receptor occupancy impatients with schizophrenia treated with therapeutic doses of ziprasidone. Am J Psychiatry 2004; 161: 818-25.CrossRefGoogle Scholar
[102]Marti, MMela, FBianchi, CBeani, LMorari, M. Striatal dopamine- NMDA receptor interactions in the modulation of glutamate release in the substantia nigra pars reticulata in vivo: opposite role for D1 and D2 receptors. J Neurochem 2002; 83: 635-44.CrossRefGoogle ScholarPubMed
[103]Matthysse, S. Antipsychotic drug actions: a clue to the neuropathology of schizophrenia? Fed Proc 1973; 32: 200-5.Google ScholarPubMed
[104]Matthysse, S. Dopamine and the pharmacology of schizophrenia: the State of the evidence. J Psychiatr Res 1974; 11: 107-13.CrossRefGoogle ScholarPubMed
[105]Mawlawi, OMartinez, DSlifstein, MBroft, AChatterjee, RHwang, DR. Imaging human mesolimbic dopamine transmission with positron emission tomography: I. Accuracy and precision of D2 receptor parameter measurements in ventral striatum. J Cereb Blood Flow Metab 2001; 21: 1034-57.CrossRefGoogle Scholar
[106]McGowan, SLawrence, ADSales, TQuested, D, Grasby R Presynaptic dopaminergic dysfunction in schizophrenia: a positron emission tomographic [l8F]fluorodopa study. Arch Gen Psychiatry 2004; 61: 134-42.Google Scholar
[107]Melis, MDiana, MGessa, GL. Clozapine potently stimulates mesocortical dopamine neurons. Eur J Pharmacol 1999; 366: R11–R13.CrossRefGoogle ScholarPubMed
[108]Meltzer, HYMatsubara, SLee, JC. Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-l, D-2, and serotonin 2 pki values. J Phammacol Exp Ther 1989; 251: 238-46.Google Scholar
[109]Meltzer, HYLi, ZKaneda, YIchikawa, J. Serotonin receptors: their key role in drugs to treat schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2003; 27: 1159-72.CrossRefGoogle ScholarPubMed
[110]Meyer-Lindenberg, AMiletich, RSKohn, PDEsposito, GCarson, REQuarantelli, M, et al. Reduced prefrontal activity predicts exaggerated striatal dopaminergic function in schizophrenia. Nat Neurosci 2002; 5: 267-71.CrossRefGoogle Scholar
[111]Miyamoto, SDuncan, GEMarx, CELieberman, JA. Treatments for schizophrenia: a critical review of pharmacology and mechanisms of action of antipsychotic drugs. Mol Psychiatry 2004 In press.CrossRefGoogle Scholar
[112]Mogenson, GJJones, DLYim, CY. From motivation to action: functional interface between the limbic System and the motor system. Prog Neurobiol 1980; 14: 69–97.CrossRefGoogle ScholarPubMed
[113]Morari, MO'Connor, WTUngerstedt, UFuxe, K. Dopamine D1 and D2 receptor antagonism differentially modulates stimulation of striatal neurotransmitter levels by A-methyl-D-aspartic acid. Eur J Pharmacol 1994; 256: 23–30.CrossRefGoogle ScholarPubMed
[114]Nicola, SMSummeier, JMalenka, RC. Dopaminergic modulation of neuronal excitability in the striatum and nucleus accumbens. Annu Rev Neurosci 2000; 23: 185–215.CrossRefGoogle ScholarPubMed
[115]Ninan, IKulkami, SK. Partial agonistic action of clozapine at dopamine D2 receptors in dopamine depleted animais. Psychopharmacology (Berlin) 1998; 35: 311-7.CrossRefGoogle Scholar
[116]Ninan, IWang, RY. Modulation of the ability of clozapine to facilitate NMDA- and electrically evoked responses in pyramidal cells of the rat medial prefrontal cortex by dopamine: pharmacological evidence. Eur J Neurosci 2003; 17: 1306-12.CrossRefGoogle ScholarPubMed
[117]Nordstrom, ALFarde, LWiesel, FAForslund, KPauli, SHalldin, C, et al. Central D2-dopamine receptor occupancy in relation to antipsychotic drug effects: a double-blind PET study of schizophrenicpatients. Biol Psychiatry 1993; 33: 227-35.CrossRefGoogle Scholar
[118]Okubo, YSahara, TSuzuki, KKobayashi, KInoue, OTerasaki, O, etal. Decreased prefrontal dopamine D1 receptors in schizophrenia revealed by PET. Nature 1997; 385: 634-6.CrossRefGoogle ScholarPubMed
[119]Olney, JWFarber, NB. Glutamate receptor dysfunction and schizophrenia. Arch Gen Psychiatry 1995; 52: 998–1007.CrossRefGoogle Scholar
[120]Onn, SPWest, ARGrate, AA. Dopamine-mediated regulation of striatal neuronal and network interactions. Trends Neurosci 2000; 23: S48-56.CrossRefGoogle ScholarPubMed
[121]Packard, MGKnowlton, BJ. Leaming and memory functions of the basal ganglio. Annu Rev Neurosci 2002; 25: 563-93.CrossRefGoogle Scholar
[122]Pantelis, CLamben, TJ. Managing patients with “treatment-resistant” schizophrenia. Med J Aust 2003; 178: S62-6.CrossRefGoogle ScholarPubMed
[123]Pehek, EAYamamoto, BK. Differential effects of locally administered clozapine and haloperidol on dopamine efflux in the rat prefrontal cortex and caudate-putamen. J Neurochem 1994; 63: 2118-24.CrossRefGoogle ScholarPubMed
[124]Peris, JDwoskin, LPZahniser, NR. Biphasic modulation of evoked [3H]D-aspartate ralease by D-2 dopamine receptors in rat striatal slices. Synapse 1988; 2: 450-6.CrossRefGoogle ScholarPubMed
[125]Pickar, DSu, TPWeinberger, DRCoppola, RMalhotra, AKKnable, MB, et al. Individual variation in D2 dopamine receptor occupancy in clozapine-treated patients. Am J Psychiatry 1996; 153: 1571-8.Google ScholarPubMed
[126]Pilowsky, LSCosta, DCEli, PJMurray, RMVerhoeff, NPKerwin, RW. Clozapine, single photon emission tomography, and the D2 dopamine receptor blockade hypothesis of schizophrenia. Lancet 1992; 340: 199–202.CrossRefGoogle ScholarPubMed
[127]Pilowsky, LSMulligan, RSActon, PDEli, PJCosta, DCKerwin, RW. Limbic selectivity of clozapine. Lancet 1997; 350: 490-1.CrossRefGoogle ScholarPubMed
[128]Pycock, CJKerwin, RWCarter, CJ. Effect of lesion of cortical dopamine terminais on subcortical dopamine receptors in rats. Nature 1980; 286: 74-7.CrossRefGoogle Scholar
[129]Reith, JBenkelfat, CSherwin, AYasuhara, YKuwabara, HAndermann, F, et al. Elevated dopa decarboxylase activity in living brain of patients with psychosis. Proc Natl Acad Sci USA 1994; 91: 11651 - 4.CrossRefGoogle ScholarPubMed
[130]Remington, G. Understanding antipsychotic “atypicality“: a clinical and pharmacological moving target. J Psychiatry Neurosci 2003; 28: 275-84.Google ScholarPubMed
[131]Remington, GKapur, SZipursky, R. The relationship between risperidone plasma levels and dopamine D-2 occupancy: a positron emission tomographic study. J Clin Psychopharmacol 1998; 18: 82-3.CrossRefGoogle Scholar
[132]Robertson, GFibiger, H. Neuroleptics increase C-fos expression in the forebrain: contrasting effects of haloperidol and clozapine. Neuroscience 1992; 46: 315-28.CrossRefGoogle ScholarPubMed
[133]Robertson, GSMatsumura, HFibiger, HC. Induction pattems of Foslike immunoreactivity in the forebrain as predictors of atypical antipsychotic activity. J Pharmacol Exp Ther 1994; 271: 1058-66.Google Scholar
[134]Rollema, HLu, YSchmidt, AWZom, SH. Clozapine increases dopamine ralease in prefrontal cortex by 5-HT1A receptor activation. Eur J Pharmacol 1997; 338: R3–R5.CrossRefGoogle ScholarPubMed
[135]Rollema, HLu, YSchmidt, AWSprouse, JSZom, SH. 5-HT(lA) receptor activation contributes to ziprasidone-induced dopamine ralease in the rat prefrontal cortex. Biol Psychiatry 2000; 48: 229-37.CrossRefGoogle ScholarPubMed
[136]Saint-Cyr, JATaylor, AENicholson, K. Behavior and the basal ganglia. Adv Neurol 1995; 65: 1–28.Google ScholarPubMed
[137]Saper, CB. Role of the cerebral cortex and striatom in emotional motor response. Prog Brain Res 1996; 107: 537-50.CrossRefGoogle ScholarPubMed
[138]Scherer, JTatsch, KSchwarz, JOertel, WKirsch, MCAlbas, M. Striatal D2-dopamine receptor occupancy during treatment with typical and atypical neuroleptics. Biol Psychiatry 1994; 36: 627- 9.CrossRefGoogle ScholarPubMed
[139]Seeger, TFSeymour, PASchmidt, AWZom, SHSchulz, DWLebel, LA, et al. Ziprasidone (CP-88,059): a new antipsychotic with combinad dopamine and serotonin receptor antagonist activity. J Phammacol Exp Ther 1995; 275: 101-3.Google ScholarPubMed
[140]Seeman, PLee, T. Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons. Science 1975; 188: 1217-9.CrossRefGoogle ScholarPubMed
[141]Shapiro, DARenock, SArrington, EChiodo, LALiu, LXSibley, DR, et al. Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology. Neuropsychopharmacology 2003; 28: 1400-11.CrossRefGoogle ScholarPubMed
[142]Smith, AD, Bolam JR The neural network of the basal ganglio as revealed by the study of synaptic connections of identified neuronas. Trends Neurosci 1990; 13: 259-65.Google Scholar
[143]Snyder, SH. Cathecolamines in the brain as mediator of amphetamine psychosis. Arch Gen Psychiatry 1972; 27: 169-79.CrossRefGoogle Scholar
[144]Starr, MS. Glutamate/dopamine D1/D2 balance in the basal ganglio and its relevance to Parkinson's disease. Synapse 1995; 19: 264-93.CrossRefGoogle Scholar
[145]Stephenson, CMBigliani, VJones, HMMulligan, RSActon, PDVisvikis, D, et al. Striatal and extra-striatal D2/D3 dopamine receptor occupancy by quetiapine in vivo. [(123)I]-epidepride single photon emission tomography(SPET) study. Br J Psychiatry 2000; 177:408-15.Google Scholar
[146]Stevens, J. An anatomy of schizophrenia? Arch Gen Psychiatry 1973; 29: 177-89.CrossRefGoogle ScholarPubMed
[147]Talvik, MNordstrom, ALNyberg, SOlsson, HHalldin, CFarde, L. No support for regional selectivity in clozapine-treated patients: a PET study with [(11)C]raclopnde and [(11)C]FLB 457. Am J Psychiatry 2001; 158: 926-30.CrossRefGoogle Scholar
[148]Tamminga, CAHolcomb, HHGao, XMLahti, AC. Glutamate pharmacology and the treatment of schizophrenia: current status and future directions. Int Clin Psychopharmacol 1995; 3: 29–37.Google Scholar
[149]Tauscher-Wisniewski, SKapur, STauscher, JJones, CDaskalakis, ZJPapatheodorou, G, et al. Quetiapine: an effective antipsychotic in first-episode schizophrenia despite only transiently high dopamine 2 receptor blockade. J Clin Psychiatry 2002; 63: 992-7.CrossRefGoogle ScholarPubMed
[150]Tsai, GYang, PChung, LCLange, NCoyle, JT. D-Serine added to antipsychotics for the treatment of schizophrenia. Biol Psychiatry 1998; 44: 1081-9.CrossRefGoogle ScholarPubMed
[151]Weinberger, DR. Implications of the normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry 1987; 44: 660-9.CrossRefGoogle ScholarPubMed
[152]Weinberger, DRLaruelle, M. Neurochemical and neuropharmacological imaging in schizophrenia. In: Davis, KLCharney, DSCoyle, JTNemeroff, C, editors. Neuropharmacology—the fifth generation of progress. Philadelphia, PA, USA: Lippincott, Williams and Wilkins; 2001.Google Scholar
[153]Weinberger, DRBerman, KFZec, RF. Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia: I. Regional Cerebral Blood flow evidence. Arch Gen Psychiatry 1986; 43: 114-24.Google Scholar
[154]Weinberger, DRBemman, KFChase, TN. Mesocortical dopaminergic function and human cognition. Ann N Y Acad Sci 1988; 537: 330-8.CrossRefGoogle ScholarPubMed
[155]West, ARGrace, AA. Opposite influences of endogenous dopamine D1 and D2 receptor activation on activity States and electrophysiological electrophysiological properties of striatal neurons: studies combining in vivo intracellular recordings and reverse microdialysis. J Neurosci 2002; 22: 294–304.CrossRefGoogle ScholarPubMed
[156]Westerink, BHKawahara, YDe Boer, PGeels, CDe Vries, JBWikstrom, HV, et al. Antipsychotic drugs classified by their effects on the release of dopamine and noradrenaline in the prefrontal cortex and striatum. Eur J Pharmacol 2001; 412: 127-38.CrossRefGoogle ScholarPubMed
[157]White, FJWang, RY. Differential effects of classical and atypical antipsychotic drugs on A9 and A10 dopamine neurons. Science 1983; 221: 1054-7.CrossRefGoogle ScholarPubMed
[158]Wiesel, FAFarde, LNordstrom, ALSedvall, G. Central D1-and D2- receptor occupancy during antipsychotic drug treatment. Prog Neuropsychop Farmacol Biol Psychiatry 1990; 14: 759-67.CrossRefGoogle ScholarPubMed
[159]Wilson, CJKawaguchi, Y. The origins of two-state spontaneous membrane potential fluctuations of neostriatal spiny neurons. J Neurosci 1996; 16: 2397-410.CrossRefGoogle ScholarPubMed
[160]Wolkin, ABarouche, FWolf, APRotrosen, JFowler, JSShiue, CY, et al. Dopamine blockade and clinical response: evidence for two biological subgroups of schizophrenia. Am J Psychiatry 1989; 146: 905-8.Google ScholarPubMed
[161]Xiberas, XMartinot, JLMallet, LArtiges, ELoc'h, CMaziere, B, et al. Extrastriatal and striatal D(2) dopamine receptor blockade with haloperidol or new antipsychotic drugs in patients with schizophrenia. Br J Psychiatry 2001; 179: 503-8.CrossRefGoogle ScholarPubMed
[162]Xiberas, XMartinot, JLMallet, LArtiges, ECanal, MLoc'h, C, et al. In vivo extrastriatal and striatal D2 dopamine receptor blockade by amisulpride in schizophrenia. J Clin Psychopharmacol 2001; 21: 207-14.CrossRefGoogle Scholar
[163]Yamamoto, BKCoopemman, MA. Differential effects of chronic antipsychotic drug treatment on extracellular glutamate and dopamine concentrations. J Neurosci 1994; 14: 4159-66.CrossRefGoogle ScholarPubMed
[164]Yasuno, FSuhara, TOkubo, YSudo, YInoue, MIchimiya, T, et al. Dose relationship of limbic-cortical D2-dopamine receptor occupancy with risperidone. Psychopharmacology (Berlin) 2001; 154: 112-4.CrossRefGoogle ScholarPubMed
[165]Yokoi, FGrander, GBiziere, KStophane, MDogan, ASDannals, RF, et al. Dopamine D2 and D3 receptor occupancy in normal humans treated with the antipsychotic drug aripiprazole (OPC 14597): a study using positron emission tomography and [“C]raclopride. Neuropsychopharmacology 2002; 27: 248-59.CrossRefGoogle Scholar
[166]Youngren, KDInglis, FMPivirotto, PJJedema, HPBradberry, CWGoldman-Rakic, PS, et al. Clozapine preferentially increases dopamine ralease in the nesus monkey prefrontal cortex compared with the caudate nucleus. Neuropsychopharmacology 1999; 20: 403-12.CrossRefGoogle Scholar