Dopamine in the Prefrontal Cortex and its Different Modulation by Conventional and Atypical Antipsychotics

Abstract

While schizophrenia seems to be associated with dopaminergic hyperactivity which can be treated with antidopaminergic drugs like the antipsychotics, dopaminergic neurotransmission in the prefrontal cortical region is unique, as its activity in schizophrenia is rather reduced. In line with many evidences that prefrontal dopamine plays an important role for cognitive functions and attention, especially working memory, prefrontal hypodopaminergic activity in schizophrenia seems to be causatively involved in the negative symptoms of the disease. Even if antipsychotics are considered as antidopaminergic drugs, conventional but much more the new atypical anti-psychotics increase prefrontal dopaminergic tone and improve to some extent negative symptoms. The pharmacological basis for this therapeutic effect is given in the present chapter.

References

• 1 Abi-Dargham A, Mawlawi O, Lombardo I, Gil R, Martinez D, Huang Y, Hwang DR, Keilp J, Kochan L, Heertum R Van, Gorman JM, Laruelle M. Prefrontal dopamine D₁ receptors and working memory in schizophrenia.  J Neurosci. 2002;  22 3708-3719
• 2 Abi-Dargham A, Moore H. Prefontal DA transmission at D₁ receptors and the pathology of schizophrenia.  Neuroscientist. 2003;  9 404-416
• 3 Ago Y, Koyama Y, Baba A, Matsuda T. Regulation by 5-HT_1A receptors of the in vivo release of 5-HT and DA in mouse frontal cortex.  Neuropharmacology. 2003;  45 1050-1056
• 4 Ago Y, Nakamura S, Baba A, Matsuda T. Sulpride in combination with fluvoxamine increases in vivo dopamine release selectively in rat prefrontal cortex.  Neuropsychopharmacology. 2005;  30 43-51
• 5 Amargós-Bosch M, Artigas F, Adell A. Effects of acute olanzapine after sustained fluoxetine on extracellular monoamine levels in the rat medial prefrontal cortex.  Eur J Pharmacol. 2005;  516 235-238
• 6 An der Heiden U. Schizophrenia as a dynamical disease.  Pharmacopsychiatry. 2006;  39 (Suppl (1)) 36-49
• 7 Andersson JL, Nomikos GG, Marcus M, Hertel P, Mathé JM, Svensson TH. Ritanserin potentiates the stimulatory effects of raclopride on neuronal activity and dopamine release selectively in the mesolimbic dopaminergic systems.  Naunyn-Schmiederberg's Arch Pharmacol. 1995;  352 374 , .385
• 8 Arnsten AF, Li BM. Neurobiology of executive function: catecholamine influences on prefrontal cortical functions.  Biol Psychiatry. 2005;  57 1377-1384
• 9 Bannon MJ, Wolf ME, Roth RH. Pharmacology of dopamine neurons innervating the prefrontal, cingulated and piriform cortices.  Eur J Pharmacol. 1983;  92 119-125
• 10 Barch DM, Sheline YI, Csernansky JG, Snyder AZ. Working memory and prefrontal cortex dysfunction. Specificity to schizophrenia compared with major depression.  Biol Psychiatry. 2003;  53 376-384
• 11 Bender W, Albus M, Möller HJ, Tretter F. Towards systemic theories in biological psychiatry.  Pharmacopsychiatry. 2006;  39 (Suppl (1)) 1-88
• 12 Bertolino A, Caforo G, Blasi G, Candia M De, Latorre V, Petruzzella V, Altamura M, Nappi G, Papa S, Callicott JH, Mattay VD, Bellomo A, Scarabino T, Weinberger DR, Nardini M. Interaction of COMT Val108/158 met genotype and olanzapine treatment on prefrontal cortical function in patients with schizophrenia.  Am J Psychiatry. 2004;  161 1798-1805
• 13 Bortolozzi A, Diaz-Mataix L, Toth M, Celada P, Antigas F. In vivo actions of aripiprazole on serotoninergic and dopaminergic systems in rodent brain.  Psychopharmacology. 2007;  191 745-758
• 14 Bortolozzi A, Diaz-Mataix L, Scorza MC, Celada P, Aritgas F. The activation of 5-HT receptors in prefrontal cortex enhances dopaminergic activity.  J Neurochem. 2005;  95 1597-1607
• 15 Bymaster FP, Zhang W, Carter PA, Show J Chernet E, Phebus L, Wong DT, Perry KW. Fluoxetine, but not other selective serotonin uptake inhibitors, increases norepinephrine and dopamine extracellular levels in prefrontal cortex.  Psychopharmacology. 2002;  160 353-361
• 16 Callicott JH, Mattay VS, Verchinski BA, Marenco S, Egan MF, Weinberger DR. Complexity of prefrontal cortical dysfunction in schizophrenia: More than up or down.  Am J Psychiatry. 2003;  160 2209-2215
• 17 Cannon TD, Glahn DC, Kim J, Erp TG Van, Karlsgodt K, Cohen MS, Nuechterlein KH, Bava D, Shirinyan D. Dorsolateral prefrontal cortex activity during maintenance and manipulation of information in working memory in patients with schizophrenia.  Arch Gen Psychiatry. 2005;  62 1071-1080
• 18 Carboni E, Silvagni A. Dopamine reuptake by norepinephrine neurons: exception or rule?.  Crit Rev Neurobiol. 2002;  16 121-128
• 19 Carlsson A. The neurochemical circuitry of schizophrenia.  Pharmacopsychiatry. 2006;  39 (Suppl (1)) 10-14
• 20 Deco G. A dynamical model of event-related fMRI signals in prefrontal cortex: Predictions for schizophrenia.  Pharmacopsychiatry. 2006;  39 (Suppl (1)) 65-67
• 21 Denys D, Klompmakers AA, Westenberg HG. Synergistic dopamine increase in the rat prefrontal cortex with the combination of quetiapine and fluvoxamine.  Psychopharmacology. 2004;  176 195-203
• 22 Devoto P, Flore G, Vacca G, Pira L, Arca A, Casu MA, Pani L, Gessa GL. Co-release of noradrenaline and dopamine from noradrenergic neurons in the cerebral cortex induced by clozapine, the prototipe atypical antipsychotic.  Psychopharmacology. 2003;  167 79-84
• 23 Diaz-Mataix L, Scorza MC, Bortolozzi A, Toth M, Celada P, Artigas F. Involvement of 5-HT_1a receptors in prefrontal cortex in the modulation of dopaminergic activity: role in atypical antipsychotic action.  J Neurosci. 2005;  25 10831-10843
• 24 Egan MF, Goldberg TE, Kolachana BS, Callicott JH, Mazzanti CM, Straub RE, Goldmann E, Weinberger DR. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia.  Proc. Natl. Acad. Sci. USA. 2001;  98 6917-6922
• 25 Elvevag B, Goldberg TE. Cognitive impairment in schizophrenia is the core of the disorder.  Crit Rev Neurobiol. 2000;  14 1-21
• 26 Emrich HM, Leweke FM, Schneider U. Systems-theory of psychosis - the relevance of “internal censorship”.  Pharmacopsychiatry. 2006;  39 (Suppl (1)) 52-53
• 27 Gobbi G, Janiri L. Clozapine blocks dopamine, 5-HT₂ and 5-HT₃ responses in the medial prefrontal cortex: an invivo microiontophoretic study.  Neuropsychopharmacology. 1999;  10 43-49
• 28 Gold JM. Cognitve deficits as treatment targets in schizophrenia.  Schizophr Res. 2004;  72 21-28
• 29 Goldberg TE, Egan MF, Geschidle T, Coppola R, Weickert T, Kolachana BS, Goldman D, Weinberger DR. Executive subprocesses in working memory: relationship to catechol-O-methyl-transferase Val158Met genotype and schizophrenia.  Arch Gen Psychiatry. 2003;  60 889-896
• 30 Goldman-Rakic PS. The cortical dopamine system: role in memory and cognition.  Adv Pharmacol. 1998;  42 707-711
• 31 Grace AA, Bunney BS, Moore H, Todd CL. Dopamine-cell depolarization block as a model for the therapeutic actions of antipsychotic drugs.  Trends Neurosci. 1997;  20 31-37
• 32 Gründer G, Vernaleken I, Müller MJ, Davids E, Heydari N, Buchholz HG, Bartenstein P, Munk OL, Stoeter P, Wong DF, Gjedde A, Cumming P. Neuropsychopharmacology. 2003;  28 787-794
• 33 Gründer G, Kungel M, Ebrecht M, Göröcs T, Modell S. Aripiprazole: Pharmacodynamics of a dopamine partial Agonist for the treatment of schizophrenia.  Pharmacopsychiatry. 2006;  39 (Suppl (1)) 21-25
• 34 Harvey PD, Green MF, Bowie C, Loebel A. The dimensions of clinical and cognitive change in schizophrenia: evidence for independence of improvements.  Psychopharmacology. 2006;  187 356-363
• 35 Hertel P, Nomikos GG, Iurio M, Svensson TH. Risperidone: regional effects in vivo on release and metabolism of dopamine and serotonin in the rat brain.  Psychopharmacology. 1996;  124 74-86
• 36 Horacek J, Bubenikova-Valesova V, Kopecek M, Palenicek T, Dockery C, Mohr P, Höschl C. Mechanism of action of atypical antipsychotic Drugs and the Neurobiology of schizophrenia.  CNS Drugs. 2006;  20 389-409
• 37 Huang M, Ichiwaka J, Li Z, Dai J, Meltzer HY. Augmentation by citalopram of risperidone-induced monoamine release in rat prefrontal cortex.  Psychopharmacology. 2006;  185 274-281
• 38 Ichikawa J, Li Z, Dai J, Meltzer HY. Atypical antipsychotic drugs, quetiapine, iloperidone, and melperone, preferentially increase dopamine and acetylcholine release in rat medial prefrontal cortex: role of 5-HT1A receptor agonism.  Brain Res. 2002;  956 349-357
• 39 Ichikawa J, Dai J, Meltzer HY. DOI, a 5-HT2A/2C receptor agonist, attenuates clozapine-induced cortical dopamine release.  Brain Res. 2001;  907 151-155
• 40 Iyer RN, Bradberry CW. Sertonin-mediated increase in prefrontal cortex dopamine release: pharmacological characterization.  J Pharmacol Exp Ther. 1996;  277 40-47
• 41 Jordan S, Kramer GL, Zukas PK, Moeller M, Petty F. In vivo biogenic amine efflux in medial prefrontal cortex with imipramine, fluoxetine, and fluvoxamine.  Synapse. 1004;  18 294-297
• 42 Kienast T, Heinz A. Dopamine and diseased brain.  CNS Neurol Disord Drug Targets. 2006;  5 109-131
• 43 Kuroki T, Meltzer HY, Ichikawa J. Effects of antipsychotic drugs on extracellular dopamine levels in rat medial prefrontal cortex and nucleus accumbens.  J Pharmacol Exp Ther. 1999;  288 774-781
• 44 Laruelle M. Dopamine transmission in the schizophrenic brain. In: Schizophrenia (eds. Hirsch, S.R., Weinberger D,) Blackwell Publishing Co. Malden, Massachusetts 2003: 365-386
• 45 Leuner K, Müller WE. The complexity of the dopamiergic synapses and their modulation by antipsychotics.  Pharmacopsychiatry. 2006;  39 (Suppl (1)) 15-20
• 46 Lewis DA, Gonzalez-Burgos G. Pathophysiologically based treatment interventions in schizophrenia.  Nat Med. 2006;  9 1016-1022
• 47 Li Z, Ichikawa J, Dai J, Meltzer HY. Aripiprazole, a novel antipsychotic drug, preferentially increases domapine release in the prefrontal cortex and hippocampus in rat brain.  Eur J Pharmacol. 2004;  493 75-83
• 48 Li Z, Ichikawa J, Huang M, Prus AJ, Dai J, Meltzer HY. ACP-103, a 5-HT2A/2C inverse agonist, potentiates haloperidol-induced dopamine release in rat medial prefrontal cortex and nucleus accumbens.  Psychopharmacology. 2005;  183 144-153
• 49 Li Z, Ichikawa J, Meltzer HY. A comparison of t he effects of loxapine with ziprasidone and thioridazine on the release of dopamine and acetylcholine in the prefrontal cortex and nucleus accumbens.  Psychopharmacology. 2004;  167 315-323
• 50 Liegeois JF, Ichikawa J, Meltzer HY. 5-HT2A receptor antagonism potentiates haloperidol-induced dopamine release in rat medial prefrontal cortex and inhibits that in the nucleus accumbens in a dose-dependent manner.  Brain Res. 2002;  947 157-165
• 51 Luciana M, Collins PF, Depue RA. Opposing roles for dopamine and serotonin in the modulation of human spatial working memory functions.  Cereb Cortex. 1998;  8 218-226
• 52 Madras BK, Miller GM, Fischman AJ. The dopamine transporter and attention-deficit/hyperactivity disorder.  Biol Psychiat. 2005;  57 1397-1409
• 53 Matsumoto M, Weicert CS, BHeltaifa S, Kolachana B, Chen J, Hyde TM, Herman MM, Weinberger DR, Kleinman JE. Catechol-O-methyltransferase COMT. mRNA expression in the dorsolateral prefrontal cortex of patients with schizophrenia.  Neuropsychopharmacology. 2003;  28 1521-1530
• 54 Mattay VS, Goldberg TE, Fera F, Hariri AR, Tessitore A, Egan MF, Kolachana B, Callicott JH, Weinberger DR. Catechol-O-methyltransferase val158-met genotype and individual variation on the brain response to amphetamine.  Proc Natl Acad Sci USA. 2003;  100 6186-6191
• 55 Mehta M, Sahakian B, MacKenna PJ, Robbins TW. Systemic sulpiride in young adult volunteers simulates the profile of cognitve deficits in Parkinson's disease.  Psychopharmacology. 1999;  146 162-174
• 56 Meyer-Lindenberg A, Nichols T, Callicott JH, Ding J, Kolachana B, Buckholtz J, Mattay VS, Egan M, Weinberger DR. Impact of complex gentic variation in COMT on human brain function.  Mol Psychiatry. 2006;  11 867-877
• 57 Meyer-Lindenberg A, Kohn PD, Kolachana B, Kippenhan S, MacInerney-Leo A, Nussbaum R, Weinberger DR, Berman KF. Midbrain dopamine and prefrontal function in humans: interaction and modulation by COMT genotype.  Nature Neuroscience. 2005;  8 594-596
• 58 Mishara AL, Goldberg TE. A meta-analysis and ciritcal review of the effects of conventional neuroleptic treatment on cognition in schizophrenia: opening a closed book.  Biol Psychiatr. 2004;  55 1013-1022
• 59 Missale C, Nash SR, Robinson SW, Jaber M, Caron MG. Dopamine receptors: from structure to function.  Physiol Rev. 1998;  78 189-225
• 60 Nakamura S, Ago Y, Itoh S, Koyama Y, Baba A, Matsuda T. Effect of zotepine on dopamine, serotonin and noradrenaline release in rat prefrontal cortex.  Eur J Pharmacol. 2005;  528 95-98
• 61 Neve KA, Seamans JK, Thrantham-Davidson H. Dopamine receptor signalling.  J. Recept Signal Transduct Res. 2004;  24 165-205
• 62 Okubo Y, Suhara T, Suzuki K, Kobayashi K, Inoue O, Terasaki O, Someya Y, Sassa T, Sudo Y, Matsushima E, Iyo M, Tateno Y, Toru M. Decreased prefrontal dopamine D₁ receptors in schizophrenia revealed by PET.  Nature. 1997;  385 634-636
• 63 Olijslagers JE, Werkman TR, MacCeary AC, Siarey R, Kruse CG, Wadman WJ. 5-HT₂ receptors differentially modulate dopamine-mediated auto-inhibition in A9 and A10 midbrain areas of the rat.  Neuropharmacology. 2004;  46 504-510
• 64 Olton DS, Becker JT, Handelmann GE. Hippocampus, time and memory.  Behav Brain. 1979;  2 313-365
• 65 Pira L, Mongeau R, Pani L. The atypical antipsychotic quetiapine increases both noradrenaline and dopamine release in the rat prefrontal cortex.  Eur J Pharmacol. 2004;  504 61-64
• 66 Phillips AG, Ahn S, Floresco SB. Magnitude of dopamine release in medial prefrontal cortex predicts accuracy of memory on a delayed response task.  J Neurosci. 2004;  24 547-553
• 67 Pozzi L, Invernizzi R, Garavaglia C, Samanin R. Fluoxetine increases extracellular dopamine in the prefrontal cortex by a mechanism not dependent on serotonin: a comparison with citalopram.  Neurochem. 1999;  73 1051-1057
• 68 Robbins TW. Chemistry of the mind: neurochemical modulation of prefrontal cortical function.  J Comp Neurol. 2005;  493 140-146
• 69 Robbins TW. From arousal to cognition: the integrative position of the prefrontal cortex.  Prog Brain Res. 2000;  126 469-483
• 70 Robbins TW. Dopamine and cognition.  Curr Opin Neurol. 2003;  16 1-2
• 71 Rollema H, Lu Y, Schmidt AW, Sprouse JS, Zorn SH. 5-HT1A receptor activation contributes to ziprasidone-induced dopamine release in the rat prefrontal cortex.  Biol Psychiatry. 2000;  48 229-237
• 72 Shifman S, Bronstein M, Sternfeld M, Pisante-Shalom A, Lev-Lehmann E, Weizman A, Reznik I, Spivak B, Grisaru N, Karp L, Schiffer R, Kotler M, Strous RD, Swartz-Vanetik M, Knobler HY, Shinar E, Beckmann JS, Yakir B, Risch N, Zak NB, Darvasi A. A highly significant association between a COMT haplotype and schizophrenia.  Am J Hum Genet. 2002;  71 1296-1302
• 73 Sesack SR, Carr DB. Selective prefrontal cortex inputs to dopamine cells: Implications for schizophrenia.  Physiol Behav. 2002;  77 513-517
• 74 Seamans JK, Floresco SB, Phillips AG. D1 receptor modulation of hippocampal prefrontal cortical circuits integrating spatial memory with executive functions in the rat.  J Neurosci. 1998;  18 1613-1621
• 75 Seamans JK, Yang CR. The principal features and mechanisms of dopamine modulation in the prefrontal cortex.  Progr Neurobiol. 2004;  1-57
• 76 Seamans JK. Working memory in the prefrontal cortex and its modulation by dopamine. In: Otani S (Ed.), Prefrontal Cortex: From Plasticity to Cognition. Kluwer, MA 2004
• 77 Seamans JK, Gorelova N, Durstewitz D, Yang CR. Bidirectional dopamine modulation of GABAergic inhibition in prefrontal cortical pyramidal neurons.  J Neurosci. 2001;  21 3628-3638
• 78 Stahl SM, Shayegan D. The psychopharmacology of Ziprasidone: receptor-binding properties and real-world psychiatric practice.  J Clin Psychiatry. 2003;  19 (Suppl 6) 6-49
• 79 Tarazi FI, Zhang K, Baldessarini RJ. Long-term effects of olanzapine, risperidone, and quetiapine on dopamine receptor types in regions of rat brain: implications for antipsychotic drug treatment.  J Pharmacol Exp Ther. 2001;  297 711-717
• 80 Tretter F, Scherer J. Schizophrenia, neurobiology and the methodology of systemic modeling.  Pharmacopsychiatry. 2006;  39 (Suppl (1)) 26-35
• 81 Ugedo L, Grenhoff J, Svensson TH. Ritanserin a 5-HT₂ receptor antagonist, activates midbrain dopamine neurons by blocking serotonergic inhibition.  Psychopharmacology. 1989;  98 45-50
• 82 Wang XJ. Toward a prefrontal microcircuit model for cognitive deficits in schizophrenia.  Pharmacopsychiatry. 2006;  39 (Suppl (1)) 80-87
• 83 Weinberger DR, Lipska B. Cortical maldevelopment, anti-psychotic drugs, and schizophrenia: a search for common ground.  Schizophr Res. 1995;  16 87-110
• 84 Werkman TR, Glennon JC, Wadman WJ, MacCreary AC. Dopamine receptor pharmacology: interactions with serotonin receptors and significance for the aetiology and treatment of schizophrenia.  CNS Neurol Disord Drug Targets. 2006;  5 3-23
• 85 Westerink BH, Vries JB De. On the mechanism of neuroleptic induced increase in striatal dopamine release: Brain dialysis provides direct evidence for mediation by autoreceptors localized on nerve terminals.  Neurosci Lett. 1989;  99 197-202
• 86 Winterer G. Cortical microcircuits in schizophrenia - the dopamine hypothesis revisited.  Pharmacopsychiatry. 2006;  39 (Suppl (1)) 68-71
• 87 Winterer G, Musso F, Vucurevic G, Stoeter P, Konrad A, Seker B, Gallinat J, Dahmen N, Weinberger DR. COMT genotype predicts BOLD signal and noise chracteristics in prefrontal circuits.  Neuroimage. 2006;  32 1722-1732
• 88 Zocchi A, Fabbri D, Heidbreder CA. Aripiprazole increases dopamine but not noradrenaline and serotonin levels in the mouse prefrontal cortex.  Neurosci Lett. 2005;  387 157-161

Correspondence