title: Effects of group I metabotropic glutamate receptor antagonists on the behavioral sensitization to motor effects of cocaine in rats.
abstract: BACKGROUND
  Metabotropic glutamate receptors (mGluRs) were reported to regulate various behavioral effects of addictive drugs.
  
  
  OBJECTIVE
  The present study evaluated the role of group I mGluRs in the progressive augmentation ("sensitization") of the behavioral effects observed after repeated, intermittent cocaine exposure.
  
  
  METHODS
  After habituation to handling and baseline activity measurement (days 1-2), rats received eight injections of cocaine (10 mg/kg) or saline on days 3-6, 8-11, and then, were tested twice with acute saline and cocaine given in a counterbalanced manner on days 13 and 15. Before the test sessions, subjects were pretreated with mGluR1 antagonist EMQMCM (JNJ16567083, (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate) and mGluR5 antagonist MTEP ([(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine).
  
  
  RESULTS
  Pretreatment with EMQMCM (2.5-10 mg/kg) but not MTEP (2.5-10 mg/kg) significantly reduced expression of the sensitized ambulatory motor activity of the cocaine-experienced animals acutely challenged with cocaine. Both EMQMCM and MTEP significantly reduced vertical motor activity across all cocaine/saline treatment conditions.
  
  
  CONCLUSIONS
  These findings indicate that the expression of behavioral sensitization to cocaine-induced stimulation of locomotor activity may be modulated by group I mGluR antagonists (mGluR1 rather than mGluR5), but these effects occur at the dose levels that attenuate vertical activity.
authors.affiliation: Laboratory of Behavioral Pharmacology, Institute of Pharmacology, Pavlov Medical University, 6/8 Lev Tolstoy Street, St Petersburg, Russia. dorav@spmu.rssi.ru
authors.forename: Olga A
authors.initials: OA
authors.lastname: Dravolina
authors.forename: Wojciech
authors.initials: W
authors.lastname: Danysz
authors.forename: Anton Y
authors.initials: AY
authors.lastname: Bespalov
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors
chemical_list: C502015:(3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxycyclohexyl)methanone methanesulfonate; C472365:3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; C578937:Grm5 protein, rat; D011725:Pyridines; D011804:Quinolines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D013844:Thiazoles; C104077:metabotropic glutamate receptor type 1; D003042:Cocaine