Preferencje help
Widoczny [Schowaj] Abstrakt
Liczba wyników
2012 | 72 | 3 |
Tytuł artykułu

Local blockade of NMDA receptors in the rat prefrontal cortex increases c_Fos expression in multiple subcortical regions

Warianty tytułu
Języki publikacji
Ketamine, phencyclidine and MK801 are uncompetitive NMDA receptor (NMDAR) antagonists which are used widely to model certain features of schizophrenia in rats. Systemic administration of NMDAR antagonists, in addition to provoking an increase in c-Fos expression, leads to important neurochemical and electrophysiological changes within the medial prefrontal cortex (mPFC). Since the mPFC is considered to exert a top-down regulatory control of subcortical brain regions, we examined the effects of local infusion of the NMDAR antagonist, MK801, into the mPFC on the expression of c-Fos protein (widely used marker of neuronal activation) in several subcortical structures. The experiment was performed on freely moving rats, bilaterally implanted with guide cannulae in the prelimbic mPFC, infused with MK801 or saline. Bilateral administration of MK801 to the mPFC produced changes in the behavior (increased stereotypy and decreased sleep-like behavior) and complex changes in c-Fos protein expression with significant increases observed in the nucleus accumbens (core and shell), amygdala (basolateral and central nuclei), the CA1 field of the hippocampus, and mediodorsal and paraventricular thalamic nuclei, as compared to the saline group. Together, we demonstrate that blockade of NMDA receptors in the mPFC is sufficient to lead to behavioral abnormalities and increased c-Fos expression in many, but not all, of the subcortical structures examined. Our findings suggest that some of the behavioral abnormalities produced by uncompetitive NMDAR antagonists may result from aberrant activity in cortico-subcortical pathways. These data support an increasing body of literature, suggesting that the mPFC is an important site mediating the effects of NMDAR antagonists.
Słowa kluczowe
Opis fizyczny
  • Department of Neurophysiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
  • Department of Neurophysiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
  • Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
  • Department of Neurophysiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
  • Department of Neurophysiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland
  • Abekawa T, Ito K, Nakagawa S, Nakato Y, Koyama T (2008) Olanzapine and risperidone block a high dose of methamphetamine-induced schizophrenia-like behavioral abnormalities and accompanied apoptosis in the medial prefrontal cortex. Schizophr Res 101: 84-94.
  • Ahn YM, Kang UG, Park JB, Kim YS (2002) Effects of MK-801 and electroconvulsive shock on c-Fos expres¬sion in the rat hippocampus and frontal cortex. Prog Neuropsychopharmacol Biol Psychiatry 26: 513-517.
  • Akirav I, Maroun M (2006) Ventromedial prefrontal cortex is obligatory for consolidation and reconsolidation of object recognition memory. Cereb Cortex 16: 1759¬1765.
  • Andine P, Widermark N, Axelsson R, Nyberg G, Olofsson U, Martensson E, Sandberg M (1999) Characterization of MK-801-induced behavior as a putative rat model of psy¬chosis. J Pharmacol Exp Ther 290: 1393-1408.
  • Arvanitogiannis A, Tzschentke TM, Riscaldino L, Wise RA, Shizgal P (2000) Fos expression following self-stimula¬tion of the medial prefrontal cortex. Behav Brain Res 107: 123-132.
  • Baviera M, Invernizzi RW, Carli M (2008) Haloperidol and clozapine have dissociable effects in a model of atten- tional performance deficits induced by blockade of NMDA receptors in the mPFC. Psychopharmacology (Berl) 196: 269-280.
  • Berretta S, Pantazopoulos H, Caldera M, Pantazopoulos P, Pare D (2005) Infralimbic cortex activation increases c-Fos expression in intercalated neurons of the amygdala. Neuroscience 132: 943-953.
  • 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: 189-199.
  • De Leonibus E, Mele A, Oliverio A, Pert A (2002) Distinct pattern of c-fos mRNA expression after systemic and intra-accumbens amphetamine and MK-801. Neuroscience 115: 67-78.
  • Del Arco A, Segovia G, Mora F (2008) Blockade of NMDA receptors in the prefrontal cortex increases dopamine and acetylcholine release in the nucleus accumbens and motor activity. Psychopharmacology (Berl) 201: 325-338.
  • Dragunow M, Faull RL (1990) MK-801 induces c-fos pro¬tein in thalamic and neocortical neurons of rat brain. Neurosci Lett 111: 39-45.
  • Feenstra MG, Botterblom MH, van Uum JF (2002) Behavioral arousal and increased dopamine efflux after blockade of NMDA-receptors in the prefrontal cortex are dependent on activation of glutamatergic neurotransmis¬sion. Neuropharmacology 42: 752-763.
  • Floresco SB, Zhang Y, Enomoto T (2009) Neural circuits subserving behavioral flexibility and their relevance to schizophrenia. Behav Brain Res 204: 396-409.
  • Geyer MA, Moghaddam B (2002) Animal models relevant to schizophrenia disorders. In: Neuropsychopharmacology: The Fifth Generation of Progress (Davis KL, Charney D, Coyle JT, Nemeroff Ch, Eds). Lippincott, Williams, & Wilkins, Philadelphia, PA. p. 689-701.
  • Gilmartin MR, Helmstetter FJ (2010) Trace and contextual fear conditioning require neural activity and NMDA receptor-dependent transmission in the medial prefrontal cortex. Learn Mem 17: 289-296.
  • Gotoh L, Kawanami N, Nakahara T, Hondo H, Motomura K, Ohta E, Kanchiku I, Kuroki T, Hirano M, Uchimura H (2002) Effects of the adenosine A(1) receptor agonist N(6)-cyclopentyladenosine on phencyclidine-induced behavior and expression of the immediate-early genes in the discrete brain regions of rats. Brain Res Mol Brain Res 100: 1-12.
  • Grace AA (2000) Gating of information flow within the limbic system and the pathophysiology of schizophrenia. Brain Res Brain Res Rev 31: 330-341.
  • Habara T, Hamamura T, Miki M, Ohashi K, Kuroda S (2001) M100907, a selective 5-HT(2A) receptor antago¬nist, attenuates phencyclidine-induced Fos expression in discrete regions of rat brain. Eur J Pharmacol 417: 189¬194.
  • Hoffman DC (1992) Typical and atypical neuroleptics antagonize MK-801-induced locomotion and stereotypy in rats. J Neural Transm Gen Sect 89: 1-10.
  • Homayoun H, Moghaddam B (2007) NMDA receptor hypo- function produces opposite effects on prefrontal cortex interneurons and pyramidal neurons. J Neurosci 27: 11496-11500.
  • Hussain N, Flumerfelt BA, Rajakumar N (2001) Glutamatergic regulation of haloperidol-induced c-fos expression in the rat striatum and nucleus accumbens. Neuroscience 102: 391-399.
  • Imre G, Fokkema DS, Den Boer JA, Ter Horst GJ (2006) Dose-response characteristics of ketamine effect on loco¬motion, cognitive function and central neuronal activity. Brain Res Bull 69: 338-345.
  • 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 U S A 101: 8467-8472.
  • Jentsch JD, Tran A, Taylor JR, Roth RH (1998) Prefrontal cortical involvement in phencyclidine-induced activation of the mesolimbic dopamine system: behavioral and neu¬rochemical evidence. Psychopharmacology (Berl) 138: 89-95.
  • Jodo E, Suzuki Y, Katayama T, Hoshino KY, Takeuchi S, Niwa S, Kayama Y (2005) Activation of medial prefron¬tal cortex by phencyclidine is mediated via a hippocam- po-prefrontal pathway. Cereb Cortex 15: 663-669.
  • Kalinichev M, Robbins MJ, Hartfield EM, Maycox PR, Moore SH, Savage KM, Austin NE, Jones DN (2008) Comparison between intraperitoneal and subcutaneous phencyclidine administration in Sprague-Dawley rats: a locomotor activity and gene induction study. Prog Neuropsychopharmacol Biol Psychiatry 32: 414-422.
  • Kargieman L, Santana N, Mengod G, Celada P, Artigas F (2008) NMDA antagonist and antipsychotic actions in cortico-subcortical circuits. Neurotox Res 14: 129-140.
  • Keilhoff G, Becker A, Grecksch G, Wolf G, Bernstein HG (2004) Repeated application of ketamine to rats induces changes in the hippocampal expression of parvalbumin, neuronal nitric oxide synthase and cFOS similar to those found in human schizophrenia. Neuroscience 126: 591¬598.
  • Koek W, Woods JH, Winger GD (1988) MK-801, a pro¬posed noncompetitive antagonist of excitatory amino acid neurotransmission, produces phencyclidine-like behav¬ioral effects in pigeons, rats and rhesus monkeys. J Pharmacol Exp Ther 245: 969-974.
  • Kovacs KJ (1998) c-Fos as a transcription factor: a stressful (re)view from a functional map. Neurochem Int 33: 287-297.
  • Lopez-Gil X, Babot Z, Amargos-Bosch M, Sunol C, Artigas F, Adell A (2007) Clozapine and haloperidol differently suppress the MK-801-increased glutamatergic and serotonergic transmission in the medial prefrontal cortex of the rat. Neuropsychopharmacology 32: 2087-2097.
  • Lorrain DS, Baccei CS, Bristow LJ, Anderson JJ, Varney MA (2003) Effects of ketamine and N-methyl-D-aspartate on glutamate and dopamine release in the rat prefrontal cortex: modulation by a group II selective metabotropic glutamate receptor agonist LY379268. Neuroscience 117: 697-706.
  • Mathe JM, Nomikos GG, Blakeman KH, Svensson TH (1999) Differential actions of dizocilpine (MK-801) on the mesolimbic and mesocortical dopamine systems: role of neuronal activity. Neuropharmacology 38: 121-128.
  • Meyza KZ, Boguszewski PM, Nikolaev E, Zagrodzka J (2007) The effect of age on the dynamics and the level of c-Fos activation in response to acute restraint in Lewis rats. Behav Brain Res 180: 183-189.
  • Meyza KZ, Boguszewski PM, Nikolaev E, Zagrodzka J. (2009) Diverse sensitivity of RHA/Verh and RLA/Verh rats to emotional and spatial aspects of a novel environ¬ment as a result of a distinct pattern of neuronal activation in the fear/anxiety circuit. Behav Genet 39: 48-61.
  • Morgan JI, Curran T (1991) Stimulus-transcription coupling in the nervous system: involvement of the inducible pro- to-oncogenes fos and jun. Annu Rev Neurosci 14: 421¬451.
  • Moser EI, Kropff E, Moser MB (2008) Place cells, grid cells, and the brain's spatial representation System. Annu Rev Neurosci 31: 69-89.
  • Mouri A, Noda Y, Enomoto T, Nabeshima T (2007) Phencyclidine animal models of schizophrenia: approach¬es from abnormality of glutamatergic neurotransmission and neurodevelopment. Neurochem Int 51: 173-184.
  • Näkki R, Sharp FR, Sagar SM, Honkaniemi J (1996) Effects of phencyclidine on immediate early gene expression in the brain. J Neurosci Res 45: 13-27.
  • Nowak K, Meyza KZ, Kasicki S, and Hunt, MJ (2009) Local blockade of NMDA receptors in the rodent prefrontal cortex modifies oscillatory activity and c-Fos expression in the nucleus accumbens. 9th International Congress of the Polish Neuroscience Society. Acta Neurobiol Exp (Wars) 69: 348.
  • Nowak K, Meyza KZ, Nikolaev E, Kasicki S and Hunt MJ (2010) Local blockade of NMDA receptors in the rodent prefrontal cortex increases c-Fos expression in multiple limbic regions. 7th FENS Forum of European Neuroscience, Amsterdam, NL.
  • O'Donnell P, Grace AA (1998) Dysfunctions in multiple interrelated systems as the neurobiological bases of schizophrenic symptom clusters. Schizophr Bull 24: 267-283.
  • Paxinos G, Watson C (1998) The Rat Brain in Stereotaxic Coordinates. Academic Press, San Diego, CA.
  • Sah P, Faber ES, Lopez De AM, Power J (2003) The amygdaloid complex: anatomy and physiology. Physiol Rev 83: 803-834.
  • Savelli JE, Chugh A, Cheng C, Mishra RK, Johnson RL (1995) Modulation of N-methyl-D-aspartate (NMDA) antagonist-induced darting behaviour by the peptidomi- metic PAMTA. Brain Res 682: 41-49.
  • Savonenko A, Filipkowski RK, Werka T, Zielinski K, Kaczmarek L (1999) Defensive conditioning-related functional heterogeneity among nuclei of the rat amygda¬la revealed by c-Fos mapping. Neuroscience 94: 723¬733.
  • Schwabe K, Koch M (2004) Role of the medial prefrontal cortex in N-methyl-D-aspartate receptor antagonist induced sensorimotor gating deficit in rats. Neurosci Lett 355: 5-8.
  • Stefani MR, Groth K, Moghaddam B (2003) Glutamate receptors in the rat medial prefrontal cortex regulate set- shifting ability. Behav Neurosci 117: 728-737.
  • Suzuki Y, Jodo E, Takeuchi S, Niwa S, Kayama Y (2002) Acute administration of phencyclidine induces tonic acti¬vation of medial prefrontal cortex neurons in freely mov¬ing rats. Neuroscience 114: 769-779.
  • Vaisanen J, Ihalainen J, Tanila H, Castren E (2004) Effects of NMDA-receptor antagonist treatment on c-fos expres¬sion in rat brain areas implicated in schizophrenia. Cell Mol Neurobiol 24: 769-780.
  • Vertes RP (2004) Differential projections of the infralimbic and prelimbic cortex in the rat. Synapse 51: 32-58.
  • Vertes RP (2006) Interactions among the medial prefrontal cortex, hippocampus and midline thalamus in emotional and cognitive processing in the rat. Neuroscience 142: 1-20.
  • Yonezawa Y, Kuroki T, Kawahara T, Tashiro N, Uchimura H (1998) Involvement of gamma-aminobutyric acid neu-rotransmission in phencyclidine-induced dopamine release in the medial prefrontal cortex. Eur J Pharmacol 341: 45-56.
  • Zuo DY, Cao Y, Zhang L, Wang HF, Wu YL (2009) Effects of acute and chronic administration of MK-801 on c-Fos protein expression in mice brain regions implicated in schizophrenia with or without clozapine. Prog Neuropsychopharmacol Biol Psychiatry 33: 290-295.
Rekord w opracowaniu
Typ dokumentu
Identyfikator YADDA
JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.