title: A Nonrewarding NMDA Receptor Antagonist Impairs the Acquisition, Consolidation, and Expression of Morphine Conditioned Place Preference in Mice.
abstract: N-methyl-D-aspartate (NMDA) receptor antagonists block morphine-induced conditioned place preference (CPP). Although polyamines are endogenous modulators of the NMDA receptor, it is not known whether polyaminergic agents induce CPP or modulate morphine-induced CPP. Here, we examined whether polyamine ligands modify morphine CPP acquisition, consolidation, and expression. Adult male albino Swiss mice received saline (0.9 % NaCl, intraperitoneally (i.p.)) or morphine (5 mg/kg, i.p.) and were respectively confined to a black or a white compartment for 30 min for four consecutive days for CPP induction. The effect of arcaine (3 mg/kg, i.p.) or spermidine (30 mg/kg, i.p.), respectively, an antagonist and an agonist of the polyamine-binding site at the NMDA receptor, on the acquisition, consolidation, and expression of morphine CPP was studied. In those experiments designed to investigate whether spermidine prevented or reversed the effect of arcaine, spermidine (30 mg/kg, i.p.) was administered 15 min before or 15 min after arcaine, respectively. Arcaine and spermidine did not induce CPP or aversion per se. Arcaine (3 mg/kg, i.p.) impaired the acquisition, consolidation, and expression of morphine CPP. Spermidine prevented the impairing effect of arcaine on the acquisition of morphine CPP but not the impairing effect of arcaine on consolidation or expression of morphine CPP. These results suggest that arcaine may impair morphine CPP acquisition by modulating the polyamine-binding site at the NMDA receptor. However, the arcaine-induced impairment of consolidation and expression of morphine CPP seems to involve other mechanisms.
authors.affiliation: Graduation Program in Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Lediane
authors.initials: L
authors.lastname: Tomazi
authors.affiliation: Graduation Program in Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Carlos Fernando
authors.initials: CF
authors.lastname: Mello
authors.affiliation: Graduation Program in Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Schöffer
authors.affiliation: Graduation Program in Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Bruna Amanda
authors.initials: BA
authors.lastname: Girardi
authors.affiliation: Graduation Program in Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Pâmella Karina Santana
authors.initials: PKS
authors.lastname: Frühauf
authors.affiliation: Graduation Program in Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil. maribel.rubin@gmail.com.|Biochemistry and Molecular Biology Department, Natural and Exact Sciences Center, Federal University of Santa Maria, Santa Maria, RS, Brazil, 97105-900. maribel.rubin@gmail.com.
authors.forename: Maribel Antonello
authors.initials: MA
authors.lastname: Rubin
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D012201:Reward
chemical_list: D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D009020:Morphine
keywords: Addiction; Arcaine; Conditioned place preference; Morphine; Spermidine