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Psychopharmacology

, Volume 214, Issue 3, pp 639–652 | Cite as

Effects of aripiprazole, olanzapine, and haloperidol in a model of cognitive deficit of schizophrenia in rats: relationship with glutamate release in the medial prefrontal cortex

  • Mirjana Carli
  • Eleonora Calcagno
  • Pierangela Mainolfi
  • Ester Mainini
  • Roberto W. Invernizzi
Original Investigation

Abstract

Rationale

Disruption in cognition is characteristic of psychiatric illnesses such as schizophrenia. Studies of drugs that improve cognition might provide a better insight into the mechanisms underlying cognitive deficits.

Objectives

We compared the effects of the antipsychotic drugs aripiprazole, olanzapine, and haloperidol on performance deficit in a test of divided and sustained visual attention, the five-choice serial reaction time task (5-CSRTT), which provides information on attentional functioning (accuracy of visual discrimination), response control (measured by anticipatory and perseverative responses) and speed.

Methods

The cognitive deficit was induced by infusion of the competitive NMDA receptor antagonist 3-(R)-2-carboxypiperazin-4-propyl-1-phosphonic acid (CPP) in the rat medial prefrontal cortex (mPFC). In vivo microdialysis was used to compare the effects of aripiprazole, olanzapine and haloperidol on CPP-induced glutamate (GLU) and serotonin (5-HT) release in the mPFC of conscious rats.

Results

Oral aripiprazole (1.0 and 3.0 mg/kg) and olanzapine (0.3 and 1.0 mg/kg), but not haloperidol (0.1 mg/kg), abolished the CPP-induced accuracy deficit and GLU release. Haloperidol and aripiprazole, but not olanzapine, reduced perseverative over-responding, while anticipatory responding was best controlled by olanzapine. However, these effects were not associated with changes in GLU release. No association was found between the effects of these antipsychotics on CPP-induced attentional performance deficits in the 5-CSRTT and 5-HT efflux.

Conclusions

The data confirm that excessive GLU release in the mPFC is associated with attentional deficits. Thus, suppression of GLU release may be a target for the development of novel antipsychotic drugs with greater effect on some aspects of cognitive deficits.

Keywords

Antipsychotics Cognitive deficits Glutamate release Medial prefrontal cortex NMDA receptor antagonists 

Notes

Acknowledgment

This work was supported by a research grant from Brystol-Myers Squibb (Italy). Olanzapine was kindly donated by Eli-Lilly and Company (USA). We are grateful to JD Baggott for language editing. The authors have nothing to disclose.

Conflicts of Interest

None

References

  1. Aghajanian GK, Marek GJ (1997) Serotonin induces excitatory postsynaptic potentials in apical dendrites of neocortical pyramidal cells. Neuropharmacology 36:589–599PubMedCrossRefGoogle Scholar
  2. Aghajanian GK, Marek GJ (1999) Serotonin, via 5-HT2A receptors, increases EPSCs in layer V pyramidal cells of prefrontal cortex by an asynchronous mode of glutamate release. Brain Res 825:161–171PubMedCrossRefGoogle Scholar
  3. Aghajanian GK, Marek GJ (2000) Serotonin model of schizophrenia: emerging role of glutamate mechanisms. Brain Res Brain Res Rev 31:302–312PubMedCrossRefGoogle Scholar
  4. Amargos-Bosch M, Bortolozzi A, Puig MV, Serrats J, Adell A, Celada P, Toth M, Mengod G, Artigas F (2004) Co-expression and in vivo interaction of serotonin1A and serotonin2A receptors in pyramidal neurons of prefrontal cortex. Cereb Cortex 14:281–299PubMedCrossRefGoogle Scholar
  5. Amargos-Bosch M, Artigas F, Adell A (2005) Effects of acute olanzapine after sustained fluoxetine on extracellular monoamine levels in the rat medial prefrontal cortex. Eur J Pharmacol 516:235–238PubMedCrossRefGoogle Scholar
  6. Amitai N, Semenova S, Markou A (2007) Cognitive-disruptive effects of the psychotomimetic phencyclidine and attenuation by atypical antipsychotic medications in rats. Psychopharmacology (Berl) 193:521–537CrossRefGoogle Scholar
  7. Assie MB, Carilla-Durand E, Bardin L, Maraval M, Aliaga M, Malfetes N, Barbara M, Newman-Tancredi A (2008) The antipsychotics clozapine and olanzapine increase plasma glucose and corticosterone levels in rats: comparison with aripiprazole, ziprasidone, bifeprunox and F15063. Eur J Pharmacol 592:160–166PubMedCrossRefGoogle Scholar
  8. Bakshi VP, Swerdlow NR, Geyer MA (1994) Clozapine antagonizes phencyclidine-induced deficits in sensorimotor gating of the startle response. J Pharmacol Exp Ther 271:787–794PubMedGoogle Scholar
  9. Baviera M, Invernizzi RW, Carli M (2008) Haloperidol and clozapine have dissociable effects in a model of attentional performance deficits induced by blockade of NMDA receptors in the mPFC. Psychopharmacology (Berl) 196:269–280CrossRefGoogle Scholar
  10. Bortolozzi A, Diaz-Mataix L, Toth M, Celada P, Artigas F (2007) In vivo actions of aripiprazole on serotonergic and dopaminergic systems in rodent brain. Psychopharmacology (Berl) 191:745–758CrossRefGoogle Scholar
  11. Breier A, Malhotra AK, Pinals DA, Weisenfeld NI, Pickar D (1997) Association of ketamine-induced psychosis with focal activation of the prefrontal cortex in healthy volunteers. Am J Psychiatry 154:805–811PubMedGoogle Scholar
  12. Bruins Slot LA, Kleven MS, Newman-Tancredi A (2005) Effects of novel antipsychotics with mixed D(2) antagonist/5-HT(1A) agonist properties on PCP-induced social interaction deficits in the rat. Neuropharmacology 49:996–1006PubMedCrossRefGoogle Scholar
  13. Burris KD, Molski TF, Xu C, Ryan E, Tottori K, Kikuchi T, Yocca FD, Molinoff PB (2002) Aripiprazole, a novel antipsychotic, is a high-affinity partial agonist at human dopamine D2 receptors. J Pharmacol Exp Ther 302:381–389PubMedCrossRefGoogle Scholar
  14. Bymaster FP, Calligaro DO, Falcone JF, Marsh RD, Moore NA, Tye NC, Seeman P, Wong DT (1996) Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuropsychopharmacology 14:87–96PubMedCrossRefGoogle Scholar
  15. Bymaster FP, Nelson DL, DeLapp NW, Falcone JF, Eckols K, Truex LL, Foreman MM, Lucaites VL, Calligaro DO (1999) Antagonism by olanzapine of dopamine D1, serotonin2, muscarinic, histamine H1 and alpha 1-adrenergic receptors in vitro. Schizophr Res 37:107–122PubMedCrossRefGoogle Scholar
  16. Calcagno E, Carli M, Invernizzi RW (2006) The 5-HT(1A) receptor agonist 8-OH-DPAT prevents prefrontocortical glutamate and serotonin release in response to blockade of cortical NMDA receptors. J Neurochem 96:853–860PubMedCrossRefGoogle Scholar
  17. Calcagno E, Carli M, Baviera M, Invernizzi RW (2009) Endogenous serotonin and serotonin2C receptors are involved in the ability of M100907 to suppress cortical glutamate release induced by NMDA receptor blockade. J Neurochem 108:521–532PubMedCrossRefGoogle Scholar
  18. Carli M, Samanin R (1992) 8-Hydroxy-2-(di-n-propylamino) tetralin impairs spatial learning in a water maze: role of postsynaptic 5-HT1A receptors. Br J Pharmacol 105:720–726PubMedGoogle Scholar
  19. Carli M, Samanin R (2000) The 5-HT1A receptor agonist 8-OH-DPAT reduces rats’ accuracy of attentional performance and enhances impulsive responding in a five-choice serial reaction time task: role of presynaptic 5-HT1A receptors. Psychopharmacology 149:259–268PubMedCrossRefGoogle Scholar
  20. Carli M, Robbins TW, Evenden JL, Everitt BJ (1983) Effects of lesions to ascending noradrenergic neurones on performance of a 5-choice serial reaction task in rats; implications for theories of dorsal noradrenergic bundle function based on selective attention and arousal. Behav Brain Res 9:361–380PubMedCrossRefGoogle Scholar
  21. Carli M, Baviera M, Invernizzi RW, Balducci C (2006) Dissociable contribution of 5-HT1A and 5-HT2A receptors in the medial prefrontal cortex to different aspects of executive control such as impulsivity and compulsive perseveration in rats. Neuropsychopharmacology 31:757–767PubMedCrossRefGoogle Scholar
  22. Ceglia I, Carli M, Baviera M, Renoldi G, Calcagno E, Invernizzi RW (2004) The 5-HT receptor antagonist M100, 907 prevents extracellular glutamate rising in response to NMDA receptor blockade in the mPFC. J Neurochem 91:189–199PubMedCrossRefGoogle Scholar
  23. Chudasama Y, Muir JL (2001) Visual attention in the rat: a role for the prelimbic cortex and thalamic nuclei? Behav Neurosci 115:417–428PubMedCrossRefGoogle Scholar
  24. Chudasama Y, Passetti F, Rhodes SE, Lopian D, Desai A, Robbins TW (2003) Dissociable aspects of performance on the 5-choice serial reaction time task following lesions of the dorsal anterior cingulate, infralimbic and orbitofrontal cortex in the rat: differential effects on selectivity, impulsivity and compulsivity. Behav Brain Res 146:105–119PubMedCrossRefGoogle Scholar
  25. Dalley JW, Theobald DE, Eagle DM, Passetti F, Robbins TW (2002) Deficits in impulse control associated with tonically-elevated serotonergic function in rat prefrontal cortex. Neuropsychopharmacology 26:716–728PubMedCrossRefGoogle Scholar
  26. DeLeon A, Patel NC, Crismon ML (2004) Aripiprazole: a comprehensive review of its pharmacology, clinical efficacy, and tolerability. Clin Ther 26:649–666PubMedCrossRefGoogle Scholar
  27. Gozzi A, Large CH, Schwarz A, Bertani S, Crestan V, Bifone A (2008) Differential effects of antipsychotic and glutamatergic agents on the phMRI response to phencyclidine. Neuropsychopharmacology 33:1690–1703PubMedCrossRefGoogle Scholar
  28. Gozzi A, Crestan V, Turrini G, Clemens M, Bifone A (2010) Antagonism at serotonin 5-HT(2A) receptors modulates functional activity of frontohippocampal circuit. Psychopharmacology (Berl) 209:37–50CrossRefGoogle Scholar
  29. Greco B, Invernizzi RW, Carli M (2005) Phencyclidine-induced impairment in attention and response control depends on the background genotype of mice: reversal by the mGLU(2/3) receptor agonist LY379268. Psychopharmacology (Berl) 179:68–76CrossRefGoogle Scholar
  30. Green MF, Marder SR, Glynn SM, McGurk SR, Wirshing WC, Wirshing DA, Liberman RP, Mintz J (2002) The neurocognitive effects of low-dose haloperidol: a 2-year comparison with risperidone. Biol Psychiatry 51:972–978PubMedCrossRefGoogle Scholar
  31. Harrison AA, Everitt BJ, Robbins TW (1997) Central 5-HT depletion enhances impulsive responding without affecting the accuracy of attentional performance: interactions with dopaminergic mechanisms. Psychopharmacology (Berl) 133:329–342CrossRefGoogle Scholar
  32. Harvey PD, Keefe RS (2001) Studies of cognitive change in patients with schizophrenia following novel antipsychotic treatment. Am J Psychiatry 158:176–184PubMedCrossRefGoogle Scholar
  33. Higgins GA, Enderlin M, Homan M, Fletcher PJ (2003) The 5-HT2A receptor antagonist M100,907 attenuates motor and “impulsive-type” behaviours produced by NMDA receptor antagonism. Psychopharmacology 170:309–319Google Scholar
  34. Hirose T, Uwahodo Y, Yamada S, Miwa T, Kikuchi T, Kitagawa H, Burris KD, Altar CA, Nabeshima T (2004) Mechanism of action of aripiprazole predicts clinical efficacy and a favourable side-effect profile. J Psychopharmacol 18:375–383PubMedCrossRefGoogle Scholar
  35. Hoffman DC, Donovan H, Cassella JV (1993) The effects of haloperidol and clozapine on the disruption of sensorimotor gating induced by the noncompetitive glutamate antagonist MK-801. Psychopharmacology (Berl) 111:339–344CrossRefGoogle Scholar
  36. Holcomb HH, Lahti AC, Medoff DR, Cullen T, Tamminga CA (2005) Effects of noncompetitive NMDA receptor blockade on anterior cingulate cerebral blood flow in volunteers with schizophrenia. Neuropsychopharmacology 30:2275–2282PubMedCrossRefGoogle Scholar
  37. Homayoun H, Moghaddam B (2007a) Fine-tuning of awake prefrontal cortex neurons by clozapine: comparison with haloperidol and N-desmethylclozapine. Biol Psychiatry 61:679–687PubMedCrossRefGoogle Scholar
  38. Homayoun H, Moghaddam B (2007b) NMDA receptor hypofunction produces opposite effects on prefrontal cortex interneurons and pyramidal neurons. J Neurosci 27:11496–11500PubMedCrossRefGoogle Scholar
  39. Homayoun H, Jackson ME, Moghaddam B (2005) Activation of metabotropic glutamate 2/3 receptors reverses the effects of NMDA receptor hypofunction on prefrontal cortex unit activity in awake rats. J Neurophysiol 93:1989–2001PubMedCrossRefGoogle Scholar
  40. Jackson ME, Homayoun H, Moghaddam B (2004) NMDA receptor hypofunction produces concomitant firing rate potentiation and burst activity reduction in the prefrontal cortex. Proc Natl Acad Sci USA 101:8467–8472PubMedCrossRefGoogle Scholar
  41. Javitt DC, Zukin SR (1991) Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry 148:1301–1308PubMedGoogle Scholar
  42. Jordan S, Chen R, Johnson J, Regardie K, Tadori Y, Kikuchi T (2002a) Aripiprazole is a potent, partial agonist at cloned human D2L and native 5-HT1A receptors. Eur Neuropsychopharmacol 13:S293CrossRefGoogle Scholar
  43. Jordan S, Koprivica V, Chen R, Tottori K, Kikuchi T, Altar CA (2002b) The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT1A receptor. Eur J Pharmacol 441:137–140PubMedCrossRefGoogle Scholar
  44. Keefe RS, Silva SG, Perkins DO, Lieberman JA (1999) The effects of atypical antipsychotic drugs on neurocognitive impairment in schizophrenia: a review and meta-analysis. Schizophr Bull 25:201–222PubMedGoogle Scholar
  45. Keefe RS, Seidman LJ, Christensen BK, Hamer RM, Sharma T, Sitskoorn MM, Lewine RR, Yurgelun-Todd DA, Gur RC, Tohen M, Tollefson GD, Sanger TM, Lieberman JA (2004) Comparative effect of atypical and conventional antipsychotic drugs on neurocognition in first-episode psychosis: a randomized, double-blind trial of olanzapine versus low doses of haloperidol. Am J Psychiatry 161:985–995PubMedCrossRefGoogle Scholar
  46. Keefe RS, Bilder RM, Davis SM, Harvey PD, Palmer BW, Gold JM, Meltzer HY, Green MF, Capuano G, Stroup TS, McEvoy JP, Swartz MS, Rosenheck RA, Perkins DO, Davis CE, Hsiao JK, Lieberman JA (2007) Neurocognitive effects of antipsychotic medications in patients with chronic schizophrenia in the CATIE Trial. Arch Gen Psychiatry 64:633–647PubMedCrossRefGoogle Scholar
  47. Kern RS, Green MF, Cornblatt BA, Owen JR, McQuade RD, Carson WH, Ali M, Marcus R (2006) The neurocognitive effects of aripiprazole: an open-label comparison with olanzapine. Psychopharmacology (Berl) 187:312–320CrossRefGoogle Scholar
  48. Kikuchi T, Tottori K, Uwahodo Y, Hirose T, Miwa T, Oshiro Y, Morita S (1995) 7-(4-[4-(2, 3-Dichlorophenyl)-1-piperazinyl]butyloxy)-3, 4-dihydro-2(1H)-quinolinone (OPC-14597), a new putative antipsychotic drug with both presynaptic dopamine autoreceptor agonistic activity and postsynaptic D2 receptor antagonistic activity. J Pharmacol Exp Ther 274:329–336PubMedGoogle Scholar
  49. Knauer CS, Campbell JE, Galvan B, Bowman C, Osgood S, Buist S, Buchholz L, Henry B, Wong EH, Shahid M, Grimwood S (2008) Validation of a rat in vivo [(3)H]M100907 binding assay to determine a translatable measure of 5-HT(2A) receptor occupancy. Eur J Pharmacol 591:136–141PubMedCrossRefGoogle Scholar
  50. Lopez-Gil X, Artigas F, Adell A (2009) Role of different monoamine receptors controlling MK-801-induced release of serotonin and glutamate in the medial prefrontal cortex: relevance for antipsychotic action. Int J Neuropsychopharmacol 12:487–499PubMedCrossRefGoogle Scholar
  51. Lucas G, Di Matteo V, De Deurwaerdere P, Porras G, Martin-Ruiz R, Artigas F, Esposito E, Spampinato U (2001) Neurochemical and electrophysiological evidence that 5-HT4 receptors exert a state-dependent facilitatory control in vivo on nigrostriatal, but not mesoaccumbal, dopaminergic function. Eur J Neurosci 13:889–898PubMedCrossRefGoogle Scholar
  52. Martin P, Waters N, Schmidt CJ, Carlsson A, Carlsson ML (1998) Rodent data and general hypothesis: antipsychotic action exerted through 5-HT2A receptor antagonism is dependent on increased serotonergic tone. J Neural Transm 105:365–396PubMedCrossRefGoogle Scholar
  53. Melendez RI, Vuthiganon J, Kalivas PW (2005) Regulation of extracellular glutamate in the prefrontal cortex: focus on the cystine glutamate exchanger and group I metabotropic glutamate receptors. J Pharmacol Exp Ther 314:139–147PubMedCrossRefGoogle Scholar
  54. Meltzer HY, McGurk SR (1999) The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia. Schizophr Bull 25:233–255PubMedGoogle Scholar
  55. Mirjana C, Baviera M, Invernizzi RW, Balducci C (2004) The serotonin 5-HT2A receptors antagonist M100907 prevents impairment in attentional performance by NMDA receptor blockade in the rat prefrontal cortex. Neuropsychopharmacology 29:1637–1647PubMedCrossRefGoogle Scholar
  56. Miyamoto Y, Yamada K, Noda Y, Mori H, Mishina M, Nabeshima T (2001) Hyperfunction of dopaminergic and serotonergic neuronal systems in mice lacking the NMDA receptor epsilon1 subunit. J Neurosci 21:750–757PubMedGoogle Scholar
  57. Moghaddam B, Adams BW (1998) Reversal of phencyclidine effects by a group II metabotropic glutamate receptor agonist in rats. Science 281:1349–1352PubMedCrossRefGoogle Scholar
  58. Moghaddam B, Jackson ME (2003) Glutamatergic animal models of schizophrenia. Ann NY Acad Sci 1003:131–137PubMedCrossRefGoogle Scholar
  59. Moghaddam B, Adams B, Verma A, Daly D (1997) Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex. J Neurosci 17:2921–2927PubMedGoogle Scholar
  60. Morimoto T, Hashimoto K, Yasumatsu H, Tanaka H, Fujimura M, Kuriyama M, Kimura K, Takehara S, Yamagami K (2002) Neuropharmacological profile of a novel potential atypical antipsychotic drug Y-931 (8-fluoro-12-(4-methylpiperazin-1-yl)-6H-[1]benzothieno[2, 3-b][1, 5] benzodiazepine maleate). Neuropsychopharmacology 26:456–467PubMedCrossRefGoogle Scholar
  61. Mukherjee J, Christian BT, Narayanan TK, Shi B, Mantil J (2001) Evaluation of dopamine D-2 receptor occupancy by clozapine, risperidone, and haloperidol in vivo in the rodent and nonhuman primate brain using 18F-fallypride. Neuropsychopharmacology 25:476–488PubMedCrossRefGoogle Scholar
  62. Nagai T, Murai R, Matsui K, Kamei H, Noda Y, Furukawa H, Nabeshima T (2009) Aripiprazole ameliorates phencyclidine-induced impairment of recognition memory through dopamine D1 and serotonin 5-HT1A receptors. Psychopharmacology (Berl) 202:315–328CrossRefGoogle Scholar
  63. Natesan S, Reckless GE, Nobrega JN, Fletcher PJ, Kapur S (2006) Dissociation between in vivo occupancy and functional antagonism of dopamine D2 receptors: comparing aripiprazole to other antipsychotics in animal models. Neuropsychopharmacology 31:1854–1863PubMedCrossRefGoogle Scholar
  64. Passetti F, Chudasama Y, Robbins TW (2002) The frontal cortex of the rat and visual attentional performance: dissociable functions of distinct medial prefrontal subregions. Cereb Cortex 12:1254–1268PubMedCrossRefGoogle Scholar
  65. Patil ST, Zhang L, Martenyi F, Lowe SL, Jackson KA, Andreev BV, Avedisova AS, Bardenstein LM, Gurovich IY, Morozova MA, Mosolov SN, Neznanov NG, Reznik AM, Smulevich AB, Tochilov VA, Johnson BG, Monn JA, Schoepp DD (2007) Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized phase 2 clinical trial. Nat Med 13:1102–1107PubMedCrossRefGoogle Scholar
  66. Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic PressGoogle Scholar
  67. Robbins TW (2002) The 5-choice serial reaction time task: behavioural pharmacology and functional neurochemistry. Psychopharmacology (Berl) 163:362–380CrossRefGoogle Scholar
  68. Robinson TE, Whishaw IQ (1988) Normalization of extracellular dopamine in striatum following recovery from a partial unilateral 6-OHDA lesion of the substantia nigra: a microdialysis study in freely moving rats. Brain Res 450:209–224PubMedCrossRefGoogle Scholar
  69. Rodefer JS, Nguyen TN, Karlsson JJ, Arnt J (2008) Reversal of subchronic PCP-induced deficits in attentional set shifting in rats by sertindole and a 5-HT6 receptor antagonist: comparison among antipsychotics. Neuropsychopharmacology 33:2657–2666PubMedCrossRefGoogle Scholar
  70. Sanchez C, Arnt J (2000) In-vivo assessment of 5-HT2A and 5-HT2C antagonistic properties of newer antipsychotics. Behav Pharmacol 11:291–298PubMedGoogle Scholar
  71. Schotte A, Janssen PF, Gommeren W, Luyten WH, Van Gompel P, Lesage AS, De Loore K, Leysen JE (1996) Risperidone compared with new and reference antipsychotic drugs: in vitro and in vivo receptor binding. Psychopharmacology (Berl) 124:57–73CrossRefGoogle Scholar
  72. Schreiber R, Brocco M, Audinot V, Gobert A, Veiga S, Millan MJ (1995) (1-(2, 5-dimethoxy-4 iodophenyl)-2-aminopropane)-induced head-twitches in the rat are mediated by 5-hydroxytryptamine (5-HT) 2A receptors: modulation by novel 5-HT2A/2C antagonists, D1 antagonists and 5-HT1A agonists. J Pharmacol Exp Ther 273:101–112PubMedGoogle Scholar
  73. Scruggs JL, Patel S, Bubser M, Deutch AY (2000) DOI-induced activation of the cortex: dependence on 5-HT2A heteroceptors on thalamocortical glutamatergic neurons. J Neurosci 20:8846–8852PubMedGoogle Scholar
  74. Scruggs JL, Schmidt D, Deutch AY (2003) The hallucinogen 1-[2, 5-dimethoxy-4-iodophenyl]-2-aminopropane (DOI) increases cortical extracellular glutamate levels in rats. Neurosci Lett 346:137–140PubMedCrossRefGoogle Scholar
  75. Shigemoto R, Kinoshita A, Wada E, Nomura S, Ohishi H, Takada M, Flor PJ, Neki A, Abe T, Nakanishi S, Mizuno N (1997) Differential presynaptic localization of metabotropic glutamate receptor subtypes in the rat hippocampus. J Neurosci 17:7503–7522PubMedGoogle Scholar
  76. Shimokawa Y, Akiyama H, Kashiyama E, Koga T, Miyamoto G (2005) High performance liquid chromatographic methods for the determination of aripiprazole with ultraviolet detection in rat plasma and brain: application to the pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci 821:8–14PubMedCrossRefGoogle Scholar
  77. Snigdha S, Neill JC (2008) Improvement of phencyclidine-induced social behaviour deficits in rats: involvement of 5-HT1A receptors. Behav Brain Res 191:26–31PubMedCrossRefGoogle Scholar
  78. Stark AD, Jordan S, Allers KA, Bertekap RL, Chen R, Mistry Kannan T, Molski TF, Yocca FD, Sharp T, Kikuchi T, Burris KD (2007) Interaction of the novel antipsychotic aripiprazole with 5-HT1A and 5-HT 2A receptors: functional receptor-binding and in vivo electrophysiological studies. Psychopharmacology (Berl) 190:373–382CrossRefGoogle Scholar
  79. Suzuki Y, Jodo E, Takeuchi S, Niwa S, Kayama Y (2002) Acute administration of phencyclidine induces tonic activation of medial prefrontal cortex neurons in freely moving rats. Neuroscience 114:769–779PubMedCrossRefGoogle Scholar
  80. Timmerman W, Westerink BH (1997) Brain microdialysis of GABA and glutamate: what does it signify? Synapse 27:242–261PubMedCrossRefGoogle Scholar
  81. Vickers SP, Easton N, Malcolm CS, Allen NH, Porter RH, Bickerdike MJ, Kennett GA (2001) Modulation of 5-HT(2A) receptor-mediated head-twitch behaviour in the rat by 5-HT(2C) receptor agonists. Pharmacol Biochem Behav 69:643–652PubMedCrossRefGoogle Scholar
  82. Vollenweider FX, Leenders KL, Oye I, Hell D, Angst J (1997a) Differential psychopathology and patterns of cerebral glucose utilisation produced by (S)- and (R)-ketamine in healthy volunteers using positron emission tomography (PET). Eur Neuropsychopharmacol 7:25–38PubMedCrossRefGoogle Scholar
  83. Vollenweider FX, Leenders KL, Scharfetter C, Antonini A, Maguire P, Missimer J, Angst J (1997b) Metabolic hyperfrontality and psychopathology in the ketamine model of psychosis using positron emission tomography (PET) and [18F]fluorodeoxyglucose (FDG). Eur Neuropsychopharmacol 7:9–24PubMedCrossRefGoogle Scholar
  84. Winstanley CA, Dalley JW, Theobald DE, Robbins TW (2004) Fractionating impulsivity: contrasting effects of central 5-HT depletion on different measures of impulsive behavior. Neuropsychopharmacology 29:1331–1343PubMedCrossRefGoogle Scholar
  85. Yang TT, Wang SJ (2008) Aripiprazole and its human metabolite OPC14857 reduce, through a presynaptic mechanism, glutamate release in rat prefrontal cortex: possible relevance to neuroprotective interventions in schizophrenia. Synapse 62:804–818PubMedCrossRefGoogle Scholar
  86. Zhang W, Bymaster FP (1999) The in vivo effects of olanzapine and other antipsychotic agents on receptor occupancy and antagonism of dopamine D1, D2, D3, 5HT2A and muscarinic receptors. Psychopharmacology (Berl) 141:267–278CrossRefGoogle Scholar
  87. Zhou FM, Hablitz JJ (1999) Activation of serotonin receptors modulates synaptic transmission in rat cerebral cortex. J Neurophysiol 82:2989–2999PubMedGoogle Scholar
  88. Zocchi A, Fabbri D, Heidbreder CA (2005) Aripiprazole increases dopamine but not noradrenaline and serotonin levels in the mouse prefrontal cortex. Neurosci Lett 387:157–161PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Mirjana Carli
    • 1
  • Eleonora Calcagno
    • 1
  • Pierangela Mainolfi
    • 1
  • Ester Mainini
    • 1
  • Roberto W. Invernizzi
    • 1
  1. 1.Laboratory of Neurochemistry and Behavior, Department of NeuroscienceIstituto di Ricerche Farmacologiche “Mario Negri”MilanItaly

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