The mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) potentiates PCP-induced cognitive deficits in rats

Psychopharmacology

Volumn 175, Issue 3, 2004, Pages 310-318

  Campbell, Una C ^a   Lalwani, Kush ^a   Hernandez, Lisa ^a   Kinney, Gene G ^b   Conn, P Jeffrey ^c   Bristow, Linda J ^a  

^a Merck Laboratories   (United States)

^b MERCK RESEARCH LABORATORIES   (United States)

^c VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Behavior; Cognition; Learning; Memory; Metabotropic glutamate receptors; MPEP; NMDA; Phencyclidine; Schizophrenia

Indexed keywords

2 METHYL 6 (PHENYLETHYNYL)PYRIDINE; METABOTROPIC RECEPTOR 5; METABOTROPIC RECEPTOR ANTAGONIST; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; PHENCYCLIDINE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BEHAVIOR; COGNITION; COGNITIVE DEFECT; CONTROLLED STUDY; HYPERACTIVITY; LEARNING DISORDER; MALE; MAZE TEST; MEMORY DISORDER; NONHUMAN; PREPULSE INHIBITION; PRIORITY JOURNAL; RAT; RAT STRAIN; SCHIZOPHRENIA; SPATIAL MEMORY;

ANIMALS; COGNITION DISORDERS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG SYNERGISM; HIPPOCAMPUS; MALE; MAZE LEARNING; MEMORY; PHENCYCLIDINE; PYRIDINES; RATS; RATS, LONG-EVANS; RECEPTORS, METABOTROPIC GLUTAMATE; RECEPTORS, N-METHYL-D-ASPARTATE;

EID: 5544228283     PISSN: 00333158     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00213-004-1827-5     Document Type: Article

References (64)

1. Adler CM, Goldberg TE, Malhotra AK, Pickar D, Breier A (1998) Effects of ketamine on thought disorder, working memory, and semantic memory in healthy volunteers. Biol Psychiatry 43:811-816
2. Alagarsamy S, Marino MJ, Rouse ST, Gereau RW IV, Heinemann SF, Conn PJ (1999) Activation of NMDA receptors reverses desensitization of mGluR5 in native and recombinant systems. Nat Neurosci 2:234-240
3. 3H]Methoxymethyl-3-[(2- methyl-1,3-thiazol-4-yl)ethynyl]pyridine binding to metabotropic glutamate receptor subtype 5 in rodent brain: in vitro and in vivo characterization. J Pharmacol Exp Ther 303:1044-1051
4. Awad H, Hubert GW, Smith Y, Levey AI, Conn PJ (2000) Activation of metabotropic glutamate receptor 5 has direct excitatory effects and potentiates NMDA receptor currents in neurons of the subthalamic nucleus. J Neurosci 20:7871-7879
5. Balschun D, Wetzel W (2002) Inhibition of mGluR5 blocks hippocampal LTP in vivo and spatial learning in rats. Pharmacol Biochem Behav 73:375-380
6. Baron SP, Moerschbaecher JM (1996) Disruption of learning by excitatory amino acid receptor antagonists. Behav Pharmacol 7:573-584
7. Breysse N, Baunez C, Spooren W, Gasparini F, Amalric M (2002) Chronic but not acute treatment with a metabotropic glutamate 5 receptor antagonist reverses the akinetic deficits in a rat model of parkinsonism. J Neurosci 22:5669-5678
8. Brodkin J, Moerschbaecher JM (1997) SR141716A antagonizes the disruptive effects of cannabinoid ligands on learning in rats. J Pharmacol Exp Ther 282:1526-1532
9. Brodkin J, Busse C, Sukoff SJ, Varney MA (2002a) Anxiolytic-like activity of the mGluR5 antagonist MPEP a comparison with diazepam and buspirone. Pharmacol Biochem Behav 73:359-366
10. Brodkin J, Bradbury M, Busse C, Warren N, Bristow LJ, Varney MA (2002b) Reduced stress-induced hyperthermia in mGluR5 knockout mice. Eur J Neurosci 16:2241-2244
11. Butelman ER (1990) The effect of NMDA antagonists in the radial arm maze task with an interposed delay. Pharmacol Biochem Behav 35:533-536
12. Campbell CM, Butelman ER, Woods JH (1999) Effects of (+)-HA-966, CGS-19755, phencyclidine, and dizocilpine on repeated acquisition of response chains in pigeons: systemic manipulation of central glycine sites. J Pharmacol Exp Ther 289:521-527
13. Chavez-Noriega LE, Schaffhauser H, Campbell UC (2002) Metabotropic glutamate receptors: potential drug targets for the treatment of schizophrenia. Curr Drug Targets-CNS Neurol Disord 1:261-281
14. Fitzjohn SM, Irving AJ, Palmer MJ, Harvey J, Lodge D, Collingridge GL (1996) Activation of group I mGluRs potentiates NMDA responses in rat hippocampal slices. Neurosci Lett 26 203:211-213
15. Goff DC, Tsai G, Manoach DS, Coyle JT (1995) Dose-finding trial of D-cycloserine added to neuroleptics for negative symptoms in schizophrenia. Am J Psychiatry 152:1213-1215
16. Goodman AB, Pardee AB (2000) Molecular neurobiological mechanisms in schizophrenia: seeking a synthesis. Biol Psychiatry 48:173-183
17. Green MF, Braff DL (2001) Translating the basic and clinical cognitive neuroscience of schizophrenia to drug development and clinical trials of antipsychotic medications. Biol Psychiatry 49:374-384
18. Henry SA, Dulawa SC, Conquet F, Geyer MA (1999) Severe disruption of prepulse inhibition in mice lacking mGluR5. Soc Neurosci Abstr 25:449
19. Henry SA, Lehmann-Masten V, Gasparini F, Geyer MA, Markou A (2002) The mGluR5 antagonist MPEP, but not the mGluR2/3 agonist LY314582, augments PCP effects on prepulse inhibition and locomotor activity. Neuropharmacology 43:1199-1209
20. Heresco-Levy U, Javitt DC, Ermilov M, Mordel C, Horowitz A, Kelly D (1996) Double-blind, placebo-controlled, crossover trial of glycine adjuvant therapy for treatment-resistant schizophrenia. Br J Psychiatry 169:610-617
21. Heresco-Levy U, Javitt DC, Ermilov M, Silipo G, Shimoni J (1998) Double-blind, placebo-controlled, crossover trial of D-cycloserine adjuvant therapy for treatment-resistant schizophrenia. Int J Neuropsychopharmcol 1:131-135
22. Heresco-Levy U, Javitt DC, Ermilov M, Mordel C, Silipo G, Lichtenstein M (1999) Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia. Arch Gen Psychiatry 56:29-36
23. Heresco-Levy U, Ermilov M, Shimoni J, Shapira B, Silipo G, Javitt DC (2002) Placebo-controlled trial of D-cycloserine added to conventional neuroleptics, olanzapine, or risperidone in schizophrenia. Am J Psychiatry 159:480-482
24. Javitt DC, Zylberman I, Zukin SR, Heresco-Levy U, Lindenmayer JP (1994) Amelioration of negative symptoms in schizophrenia by glycine. Am J Psychiatry 151:1234-1236
25. Jentsch JD, Roth RH (1999) The neuropsychopharmacology of phencyclidine: from NMDA receptor hypofunction to the dopamine hypothesis of schizophrenia. Neuropsychopharmacology 20:201-225
26. Jia Z, Lu Y, Henderson J, Taverna F, Romano C, Abramow-Newerly W, Wojtowicz JM, Roder J (1998) Selective abolition of the NMDA component of long-term potentiation in mice lacking mGluR5. Learn Mem 5:331-343
27. 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 25:201-222
28. Kinney GG, Burno M, Campbell UC, Hernandez LM, Rodriguez D, Bristow LJ, Conn PJ (2003) Metabotropic glutamate subtype 5 receptors (mglur5) modulate locomotor activity and sensorimotor gating in rodents. J Pharmacol Exp Ther 306:116-123
29. Krystal JH, Karper LP, Seibyl JP, Freeman GK, Delaney R, Bremner JD, Heninger GR, Bowers MB Jr, Charney DS (1994) Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry 51:199-214
30. Lahti AC, Weiler MA, Tamara Michaelidis BA, Parwani A, Tamminga CA (2001) Effects of ketamine in normal and schizophrenic volunteers. Neuropsychopharmacology 25:455-467
31. Lieberman JA, Perkins D, Beiger A, Chakos M, Jarskog F, Boteva K, Gilmore J (2001) The early stages of schizophrenia: speculations on pathogenesis, pathophysiology, and therapeutic approaches. Biol Psychiatry 50:884-897
32. Lu YM, Jia Z, Janus C, Henderson JT, Gerlai R, Wojtowicz JM, Roder JC (1997) Mice lacking metabotropic glutamate receptor 5 show impaired learning and reduced CA1 long-term potentiation (LTP) but normal CA3 LTP. J Neurosci 17:5196-5205
33. Lujan R, Nusser Z, Roberts JD, Shigemoto R, Somogyi P (1996) Perisynaptic location of metabotropic glutamate receptors mGluR1 and mGluR5 on dendrites and dendritic spines in the rat hippocampus. Eur J Neurosci 8:1488-1500
34. Malhotra AK, Pinals DA, Weingartner H, Sirocco K, Missar CD, Pickar D, Breier A (1996) NMDA receptor function and human cognition: the effects of ketamine in healthy volunteers. Neuropsychopharmacology 14:301-307
35. Malhotra AK, Pinals DA, Adler CM, Elman I, Clifton A, Pickar D, Breier A (1997) Ketamine-induced exacerbation of psychotic symptoms and cognitive impairment in neuroleptic-free schizophrenics. Neuropsychopharmacology 17:141-150
36. Mannaioni G, Marino MJ, Valenti O, Traynelis SF, Conn PJ (2001) Metabotropic glutamate receptors 1 and 5 differentially regulate CA1 pyramidal cell function. J Neurosci 21:5925-5934
37. Marino MG, Conn PJ (2002) Direct and indirect modulation of the N-methyl-D-aspartate receptor: potential for the development of novel antipsychotic therapies. Curr Drug Targets-CNS Neurol Disord 1:1-16
38. Meltzer HY (1999) Treatment of schizophrenia and spectrum disorders: pharmacotherapy, psychosocial treatments, and neurotransmitter interactions. Biol Psychiatry 46:1321-1327
39. Meltzer HY, McGurk SR (1999) The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia. Schizophr Bull 25:233-255
40. Moerschbaecher JM, Mastropaolo J, Winsauer PJ, Thompson DM (1984) Effects of opioids on accuracy of a fixed-ratio discrimination in monkeys and rats. J Pharmacol Exp Ther 230:541-549
41. National Research Council (1996) Guide for the care and use of laboratory animals. National Academy Press, Washington D.C.
42. Newcomer JW, Farber NB, Jevtovic-Todorovic V, Selke G, Melson AK, Hershey T, Craft S, Olney JW (1999) Ketamine-induced NMDA receptor hypofunction as a model of memory impairment and psychosis. Neuropsychopharmacology 20:106-118
43. Olney JW, Newcomer JW, Farber NB (1999) NMDA receptor hypofunction model of schizophrenia. J Psychiatr Res 33:523-533
44. O'Leary DM, Movsesyan V, Vicini S, Faden AI (2000) Selective mGluR5 antagonists MPEP and SIB-1893 decrease NMDA or glutamate-mediated neuronal toxicity through actions that reflect NMDA receptor antagonism. Br J Pharmacol 131:1429-1437
45. O'Meara GF, Newman RJ, Reynolds DS, Bristow LJ, Dawson GR (2002) Behavioral evaluation of mGluR5 knockout mouse. FENS Abstr 1:A087.6
46. Ossowska K, Konieczny J, Wolfarth S, Wieronska J, Pile A (2001) Blockade of the metabotropic glutamate receptor subtype 5 (mGluR5) produces antiparkinsonian-like effects in rats. Neuropharmacology 41:413-420
47. Petersen S, Bomme C, Baastrup C, Kemp A, Christoffersen GR (2002) Differential effects of mGluR1 and mGlur5 antagonism on spatial learning in rats. Pharmacol Biochem Behav 73:381-389
48. Pile A, Klodzinska A, Branski P, Nowak G, Palucha A, Szewczyk B, Tatarczynska E, Chojnacka-Wojcik E, Wieronska JM (2002) Multiple MPEP administrations evoke anxiolytic- and antidepressant-like effects in rats. Neuropharmacology 43:181-187
49. Pisani A, Gubellini P, Bonsi P, Conquet F, Picconi B, Centonze D, Bernardi G, Calabresi P (2001) Metabotropic glutamate receptor 5 mediates the potentiation of N-methyl-D-aspartate responses in medium spiny striatal neurons. Neuroscience 106: 579-587
50. Popik P, Wrobel M (2002) Morphine conditioned reward is inhibited by MPEP, the mGluR5 antagonist. Neuropharmacology 43:1210-1217
51. Romano C, Sesma MA, McDonald CT, O'Malley K, Van den Pol AN, Olney JW (1995) Distribution of metabotropic glutamate receptor mGluR5 immunoreactivity in rat brain. J Comp Neurol 355:455-469
52. Sharma T (1999) Cognitive effects of conventional and atypical antipsychotics in schizophrenia. Br J Psychiatry Suppl 38:44-51
53. Sharma T, Antonova L (2003) Cognitive function in schizophrenia. Deficits, functional consequences, and future treatment. Psychiatr Clin N Am 26:25-40
54. Shigemoto R, Nomura S, Ohishi H, Sugihara H, Nakanishi S, Mizuno N (1993) Immunohistochemical localization of a metabotropic glutamate receptor, mGluR5, in the rat brain. Neurosci Lett 26 163:53-57
55. 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 17:7503-7522
56. Spooren WP, Vassout A, Neijt HC, Kuhn R, Gasparini F, Roux S, Porsolt RD, Gentsch C (2000) Anxiolytic-like effects of the prototypical metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)pyridine in rodents. J Pharmacol Exp Ther 295:1267-1275
57. Spooren WP, Schoeffter P, Gasparini F, Kuhn R, Gentsch C (2002) Pharmacological and endocrinological characterisation of stress-induced hyperthermia in singly housed mice using classical and candidate anxiolytics (LY314582, MPEP and NKP608). Eur J Pharmacol 435:161-170
58. Stip E (1996) Memory impairment in schizophrenia: perspectives from psychopathology and pharmacotherapy. Can J Psychiatry 41:827-34
59. Tamminga CA, Buchanan RW, Gold JM (1998) The role of negative symptoms and cognitive dysfunction in schizophrenia outcome. Int Clin Psychopharmacol 13:821-26
60. Tatarczynska E, Klodzinska A, Chojnacka-Wojcik E, Palucha A, Gasparini F, Kuhn R, Pile A (2001) Potential anxiolytic- and antidepressant-like effects of MPEP, a potent, selective and systemically active mGlu5 receptor antagonist. Br J Pharmacol 132:1423-1430
61. Thompson DM, Moerschbaecher JM (1979) An experimental analysis of the effects of D-amphetamine and cocaine on the acquisition and performance of response chains in monkeys. J Exp Anal Behav 32:433-444
62. Wieronska JM, Szewczyk B, Branski P, Palucha A, Pile A (2002) Antidepressant-like effect of MPEP, a potent, selective and systemically active mGlu5 receptor antagonist in the olfactory bulbectomized rats. Amino Acids 23:213-216
63. Winsauer PJ, Bixler MA, Mele PC (1996) Comparison of the effects of typical and atypical anxiolytics on learning in monkeys and rats. J Pharmacol Exp Ther 276:1111-1127
64. Winsauer PJ, Rodriguez FH, Cha AE, Moerschbaecher JM (1999) Full and partial 5-HT1A receptor agonists disrupt learning and performance in rats. J Pharmacol Exp Ther 288:335-347