title: Pretreatment with morphine potentiates naloxone-conditioned place aversion in mice: effects of NMDA receptor antagonists.
abstract: Acute pretreatment with opioid receptor agonists potentiates behavioral effects of opioid antagonists. This phenomenon was suggested to serve as an acute model of opioid dependence. Since antagonists acting at N-methyl-D-aspartate (NMDA) receptors were repeatedly shown to attenuate development, maintenance, and expression of opioid dependence, the present study evaluated the effects of competitive NMDA receptor antagonist, D-CPPene (SDZ EAA 494; 3-(2-carboxypiperazin-4-yl)-1-propenyl-1-phosphonic acid), and low-affinity channel blocker, 1-amino-3,5-dimethyl adamantane hydrochloride (memantine), on establishment of naloxone-conditioned place aversion in mice that were pre-exposed to morphine. Morphine (20 mg/kg) pretreatment significantly potentiated the ability of naloxone (0.01-0.3 mg/kg) to produce place aversion. The place aversion produced by naloxone (0.1 mg/kg) was attenuated by D-CPPene (1 and 3 mg/kg but not 0.1 or 0.3 mg/kg) when it was administered 3.5 h after morphine (0.5 h prior to conditioning trial with naloxone) but not 0.5 h prior to morphine. Memantine (1-10 mg/kg) had no effect under any treatment condition (0.5 h prior to morphine, simultaneously with morphine, 2 or 3.5 h after morphine). Thus, the ability of NMDA receptor antagonist to affect development and/or expression of morphine dependence may not be a good predictor of their effects on establishment of morphine-potentiated naloxone-conditioned place aversion.
authors.affiliation: Laboratory of Behavioral Pharmacology, Valdman Institute of Pharmacology, Pavlov Medical University, 6/8 Lev Tolstoy St., 197089, Saint Petersburg, Russia.
authors.forename: E A
authors.initials: EA
authors.lastname: Blokhina
authors.forename: I A
authors.initials: IA
authors.lastname: Sukhotina
authors.forename: A Y
authors.initials: AY
authors.lastname: Bespalov
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D008559:Memantine / Q000494:pharmacology; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D009292:Narcotic Antagonists; D009294:Narcotics; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; C065286:SDZ EAA 494; D009270:Naloxone; D009020:Morphine; D008559:Memantine