Related Experiment Video
Updated: Apr 27, 2026
HSV-Mediated Transgene Expression of Chimeric Constructs to Study Behavioral Function of GPCR Heteromers in Mice
Published on: July 9, 2016
mGluR5 positive allosteric modulation and its effects on MK-801 induced set-shifting impairments in a rat operant
Amber L LaCrosse1, Brian T Burrows, Rachel M Angulo
1Department of Psychology, Arizona State University, Tempe, AZ, USA, alacross@asu.edu.
Rationale:
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.
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.
