title: Effect of glutamate receptor antagonists on place aversion induced by naloxone in single-dose morphine-treated rats.
abstract: The neurobiological mechanism underlying the negative motivational component of withdrawal from acute opiate dependence is far from understood. Our objectives were to determine whether the glutamatergic system is involved in the motivational component of morphine withdrawal in acutely dependent rats and such an involvement is associated with dopaminergic neurotransmission. We examined the effects of various kinds of glutamate receptor antagonists on conditioned place aversion (CPA) induced by naloxone-precipitated withdrawal from a single morphine exposure 24 h before. Furthermore, the influence of pretreatment with the dopamine receptor antagonist haloperidol on those effects of glutamate receptor antagonists was also investigated. CPA was attenuated in a dose-dependent manner by all glutamate receptor antagonists examined including the NMDA receptor antagonists (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclo-hepten-5,10-imine maleate (MK-801) and phencyclidine hydrochloride (PCP), AMPA receptor antagonist 1-(4-aminophenyl)4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride (GYKI 52466), and metabotropic receptor antagonists (+/-)-2-amino-3-phosphonopropionic acid (AP-3) and (+/-)-alpha-methyl-4-carboxyphenylglycine (MCPG). The effects of MK-801, GYKI 52466 and MCPG were blocked by haloperidol. These results suggest that the glutamatergic system involving multiple classes of receptors plays a role in the motivational component of withdrawal from acute morphine dependence, and the function of the glutamatergic system would be closely associated with dopaminergic neurotransmission.
authors.affiliation: Department of Hospital Pharmacy, Okayama University Medical School, 2-5-1, Shikata-cho, Okayama 700-8558, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kawasaki
authors.forename: Chunyu
authors.initials: C
authors.lastname: Jin
authors.forename: Katsuya
authors.initials: K
authors.lastname: Suemaru
authors.forename: Hiromu
authors.initials: H
authors.lastname: Kawasaki
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Shibata
authors.forename: Tominari
authors.initials: T
authors.lastname: Choshi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hibino
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Gomita
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Araki
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D003213:Conditioning, Psychological; D018492:Dopamine Antagonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000008:administration & dosage; D009021:Morphine Dependence / Q000378:metabolism / Q000523:psychology*; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009294:Narcotics / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D009020:Morphine; D006220:Haloperidol