title: 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.
abstract: BACKGROUND
  Positive allosteric modulators (PAMs) of type 5 metabotropic glutamate receptors (mGluR5) exert pro-cognitive 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.
  
  
  OBJECTIVE
  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.
authors: Department of Psychology, Arizona State University, Tempe, AZ, USA, alacross@asu.edu.
authors: Amber L
authors: AL
authors: LaCrosse
authors: Brian T
authors: BT
authors: Burrows
authors: Rachel M
authors: RM
authors: Angulo
authors: Phoebe R
authors: PR
authors: Conrad
authors: Sarah M
authors: SM
authors: Himes
authors: Nordia
authors: N
authors: Mathews
authors: Scott A
authors: SA
authors: Wegner
authors: Sara B
authors: SB
authors: Taylor
authors: M Foster
authors: MF
authors: Olive
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D007858:Learning / Q000187:drug effects / Q000502:physiology; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects* / Q000502:physiology*; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: C494553:3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide; D001549:Benzamides; D011720:Pyrazoles; D064529:Receptor, Metabotropic Glutamate 5; D016291:Dizocilpine Maleate