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.
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 mGluR5PAM3-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: John H Krystal; Sanjay J Mathew; D Cyril D'Souza; Amir Garakani; Handan Gunduz-Bruce; Dennis S Charney Journal: CNS Drugs Date: 2010-08 Impact factor: 5.749
Authors: Gene G Kinney; Julie A O'Brien; Wei Lemaire; Maryann Burno; Denise J Bickel; Michelle K Clements; Tsing-Bau Chen; David D Wisnoski; Craig W Lindsley; Philip R Tiller; Sheri Smith; Marlene A Jacobson; Cyrille Sur; Mark E Duggan; Douglas J Pettibone; P Jeffrey Conn; David L Williams Journal: J Pharmacol Exp Ther Date: 2004-12-17 Impact factor: 4.030
Authors: Gary Gilmour; Lisa M Broad; Keith A Wafford; Thomas Britton; Ellen M Colvin; Adam Fivush; Francois Gastambide; Brian Getman; Beverly A Heinz; Andrew P McCarthy; Lourdes Prieto; Elaine Shanks; Janice W Smith; Lorena Taboada; Dale M Edgar; Mark D Tricklebank Journal: Neuropharmacology Date: 2012-08-01 Impact factor: 5.250
Authors: Fukang Yang; Lawrence B Snyder; Anand Balakrishnan; Jeffrey M Brown; Digavalli V Sivarao; Amy Easton; Alda Fernandes; Michael Gulianello; Umesh M Hanumegowda; Hong Huang; Yanling Huang; Kelli M Jones; Yu-Wen Li; Michele Matchett; Gail Mattson; Regina Miller; Kenneth S Santone; Arun Senapati; Eric E Shields; Frank J Simutis; Ryan Westphal; Valerie J Whiterock; Joanne J Bronson; John E Macor; Andrew P Degnan Journal: ACS Med Chem Lett Date: 2016-01-04 Impact factor: 4.345
Authors: Amber L LaCrosse; Sara B Taylor; Natali E Nemirovsky; Justin T Gass; Michael F Olive Journal: CNS Neurol Disord Drug Targets Date: 2015 Impact factor: 4.388
Authors: Kimberly A Badanich; Mackinzie E Fakih; Tatyana S Gurina; Emalie K Roy; Jessica L Hoffman; Adriana R Uruena-Agnes; Cheryl L Kirstein Journal: Psychopharmacology (Berl) Date: 2016-08-12 Impact factor: 4.530