mGluR5 positive allosteric modulation and its effects on MK-801 induced set-shifting impairments in a rat operant delayed matching/non-matching-to-sample task

Amber L. LaCrosse, Brian T. Burrows, Rachel M. Angulo, Phoebe R. Conrad, Sarah M. Himes, Nordia Mathews, Scott A. Wegner, Sara B. Taylor, Michael Olive

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Rationale: Positive allosteric modulators (PAMs) of type 5 metabotropic glutamate receptors (mGluR5) exert procognitive effects in animal models of various neuropsychiatric diseases. However, few studies to date have examined ability of mGluR5 PAMs to reverse cognitive deficits in operant delayed matching/non-matching-to-sample (DMS/DNMS) tasks. Objectives: This study aims to determine the ability of the mGluR5 PAM 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) to reverse set-shifting deficits induced by the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801. Methods: Male Sprague-Dawley rats were initially trained to lever press for sucrose reinforcement under either DMS or DNMS conditions. Following successful acquisition of the task, reinforcement conditions were reversed (DNMS → DMS or DMS → DNMS). In Experiment 1, rats were treated daily prior to each session with vehicle/vehicle, vehicle/MK-801 (0.06 mg/kg) simultaneously, CDPPB (20 mg/kg)/MK-801 simultaneously, or CDPPB 30 min prior to MK-801. In Experiment 2, rats were treated with either vehicle/vehicle, vehicle/MK-801, or CDPPB 30 min prior to MK-801 only prior to sessions that followed task reversal. Results: In Experiment 1, no group differences in initial task acquisition were observed. Rats treated with vehicle/MK-801 showed significant set-shifting impairments following task reversal, which were partially attenuated by simultaneous administration of CDPPB/MK-801 and completely precluded by administration of CDPPB 30 min prior to MK-801. In Experiment 2, MK-801 did not impair reversal learning, and no other group differences were observed. Conclusions: MK-801-induced deficits in operant set-shifting ability were prevented by pretreatment with CDPPB. MK-801 did not produce deficits in task learning when treatment was initiated following task reversal.

Original languageEnglish (US)
Pages (from-to)251-258
Number of pages8
JournalPsychopharmacology
Volume232
Issue number1
DOIs
StatePublished - 2015

Fingerprint

Dizocilpine Maleate
Aptitude
Metabotropic Glutamate 5 Receptor
Reversal Learning
3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide
N-Methyl-D-Aspartate Receptors
Sprague Dawley Rats
Sucrose
Animal Models
Learning

Keywords

  • Cognitive impairment
  • Match-to-sample
  • N-methyl-D-aspartate receptor
  • Operant set-shifting
  • Schizophrenia
  • Type 5metabotropic glutamate receptor

ASJC Scopus subject areas

  • Pharmacology

Cite this

mGluR5 positive allosteric modulation and its effects on MK-801 induced set-shifting impairments in a rat operant delayed matching/non-matching-to-sample task. / LaCrosse, Amber L.; Burrows, Brian T.; Angulo, Rachel M.; Conrad, Phoebe R.; Himes, Sarah M.; Mathews, Nordia; Wegner, Scott A.; Taylor, Sara B.; Olive, Michael.

In: Psychopharmacology, Vol. 232, No. 1, 2015, p. 251-258.

Research output: Contribution to journalArticle

LaCrosse, Amber L. ; Burrows, Brian T. ; Angulo, Rachel M. ; Conrad, Phoebe R. ; Himes, Sarah M. ; Mathews, Nordia ; Wegner, Scott A. ; Taylor, Sara B. ; Olive, Michael. / mGluR5 positive allosteric modulation and its effects on MK-801 induced set-shifting impairments in a rat operant delayed matching/non-matching-to-sample task. In: Psychopharmacology. 2015 ; Vol. 232, No. 1. pp. 251-258.
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abstract = "Rationale: Positive allosteric modulators (PAMs) of type 5 metabotropic glutamate receptors (mGluR5) exert procognitive effects in animal models of various neuropsychiatric diseases. However, few studies to date have examined ability of mGluR5 PAMs to reverse cognitive deficits in operant delayed matching/non-matching-to-sample (DMS/DNMS) tasks. Objectives: This study aims to determine the ability of the mGluR5 PAM 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) to reverse set-shifting deficits induced by the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801. Methods: Male Sprague-Dawley rats were initially trained to lever press for sucrose reinforcement under either DMS or DNMS conditions. Following successful acquisition of the task, reinforcement conditions were reversed (DNMS → DMS or DMS → DNMS). In Experiment 1, rats were treated daily prior to each session with vehicle/vehicle, vehicle/MK-801 (0.06 mg/kg) simultaneously, CDPPB (20 mg/kg)/MK-801 simultaneously, or CDPPB 30 min prior to MK-801. In Experiment 2, rats were treated with either vehicle/vehicle, vehicle/MK-801, or CDPPB 30 min prior to MK-801 only prior to sessions that followed task reversal. Results: In Experiment 1, no group differences in initial task acquisition were observed. Rats treated with vehicle/MK-801 showed significant set-shifting impairments following task reversal, which were partially attenuated by simultaneous administration of CDPPB/MK-801 and completely precluded by administration of CDPPB 30 min prior to MK-801. In Experiment 2, MK-801 did not impair reversal learning, and no other group differences were observed. Conclusions: MK-801-induced deficits in operant set-shifting ability were prevented by pretreatment with CDPPB. MK-801 did not produce deficits in task learning when treatment was initiated following task reversal.",
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AU - Burrows, Brian T.

AU - Angulo, Rachel M.

AU - Conrad, Phoebe R.

AU - Himes, Sarah M.

AU - Mathews, Nordia

AU - Wegner, Scott A.

AU - Taylor, Sara B.

AU - Olive, Michael

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N2 - Rationale: Positive allosteric modulators (PAMs) of type 5 metabotropic glutamate receptors (mGluR5) exert procognitive effects in animal models of various neuropsychiatric diseases. However, few studies to date have examined ability of mGluR5 PAMs to reverse cognitive deficits in operant delayed matching/non-matching-to-sample (DMS/DNMS) tasks. Objectives: This study aims to determine the ability of the mGluR5 PAM 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) to reverse set-shifting deficits induced by the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801. Methods: Male Sprague-Dawley rats were initially trained to lever press for sucrose reinforcement under either DMS or DNMS conditions. Following successful acquisition of the task, reinforcement conditions were reversed (DNMS → DMS or DMS → DNMS). In Experiment 1, rats were treated daily prior to each session with vehicle/vehicle, vehicle/MK-801 (0.06 mg/kg) simultaneously, CDPPB (20 mg/kg)/MK-801 simultaneously, or CDPPB 30 min prior to MK-801. In Experiment 2, rats were treated with either vehicle/vehicle, vehicle/MK-801, or CDPPB 30 min prior to MK-801 only prior to sessions that followed task reversal. Results: In Experiment 1, no group differences in initial task acquisition were observed. Rats treated with vehicle/MK-801 showed significant set-shifting impairments following task reversal, which were partially attenuated by simultaneous administration of CDPPB/MK-801 and completely precluded by administration of CDPPB 30 min prior to MK-801. In Experiment 2, MK-801 did not impair reversal learning, and no other group differences were observed. Conclusions: MK-801-induced deficits in operant set-shifting ability were prevented by pretreatment with CDPPB. MK-801 did not produce deficits in task learning when treatment was initiated following task reversal.

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KW - Match-to-sample

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KW - Operant set-shifting

KW - Schizophrenia

KW - Type 5metabotropic glutamate receptor

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