title: The mGluR5 antagonist MPEP suppresses the expression and reinstatement, but not the acquisition, of the ethanol-conditioned place preference in mice.
abstract: The glutamatergic system may play a vital role in regulating neurobehavioral effects of various drugs of abuse. In the present study, we evaluated the effects of 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a selective antagonist of the type 5 metabotropic glutamate receptor (mGluR5) on the acquisition, expression and reinstatement of ethanol conditioned place preference (CPP). In the ethanol acquisition study, mice were conditioned with saline or ethanol (20% v/v, 2g/kg) on alternating days for 8 consecutive days and were given MPEP 10 min before ethanol conditioning. In another experiment, animals were conditioned with 2g/kg ethanol and MPEP was administered 10 min prior to the post-conditioning test. In a reinstatement study, following the extinction phase, animals were pretreated with MPEP 10 min prior to a priming injection of 1.0 g/kg ethanol. The mGluR5 antagonist MPEP significantly reduced the expression and the reinstatement in dose-dependent manner, but not acquisition of ethanol-induced CPP. These results indicate that mGluR5 may be involved in the expression and reinstatement of conditioned rewarding effects of ethanol, but not the acquisition of ethanol, which provide an evidence that mGluR5 blockade might make dissociable contributions during the training (acquisition phase), the performance of behavior (expression phase) and reinstatement.
authors.affiliation: Research Center for Safety Pharmacology, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea; Department of Toxicology Evaluation, Konyang University, Daejeon 35365, Republic of Korea.
authors.forename: Jun-Yeob
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Pusan National University, Busan 46241, Republic of Korea.
authors.forename: Eun Sang
authors.initials: ES
authors.lastname: Choe
authors.affiliation: Department of Physiology, College of Oriental Medicine, Daegu Haany University, Daegu 42158, Republic of Korea.
authors.forename: Chae Ha
authors.initials: CH
authors.lastname: Yang
authors.affiliation: Department of Psychiatry and Program in Neuroscience, Center for the Study of Traumatic Stress, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, United States.
authors.forename: Kwang H
authors.initials: KH
authors.lastname: Choi
authors.affiliation: Uimyung Research Institute for Neuroscience, School of Pharmacy, Sahmyook University, 26-21 Kongreung-2-dong, Hwarangro-815, Nowon-gu, Seoul 01795, Republic of Korea.
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Cheong
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
authors.forename: Choon-Gon
authors.initials: CG
authors.lastname: Jang
authors.affiliation: Research Center for Safety Pharmacology, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea. Electronic address: jwseo@kitox.re.kr.
authors.forename: Joung-Wook
authors.initials: JW
authors.lastname: Seo
authors.affiliation: Research Center for Safety Pharmacology, Korea Institute of Toxicology, Daejeon 34114, Republic of Korea. Electronic address: ssyoon@kitox.re.kr.
authors.forename: Seong Shoon
authors.initials: SS
authors.lastname: Yoon
mesh_terms: D000428:Alcohol Drinking / Q000523:psychology*; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011725:Pyridines / Q000494:pharmacology*; D064529:Receptor, Metabotropic Glutamate 5 / Q000037:antagonists & inhibitors*; D012201:Reward
chemical_list: D002492:Central Nervous System Depressants; D018691:Excitatory Amino Acid Antagonists; C578936:Grm5 protein, mouse; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D000431:Ethanol; C121465:6-methyl-2-(phenylethynyl)pyridine
keywords: Conditioned place preference; Ethanol; MPEP; Mice; Rewarding effects; mGluR5