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1.
Mol Neurobiol ; 54(1): 710-721, 2017 01.
Article in English | MEDLINE | ID: mdl-26768427

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.


Subject(s)
Analgesics, Opioid/administration & dosage , Conditioning, Classical/drug effects , Excitatory Amino Acid Antagonists/pharmacology , Morphine/administration & dosage , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors , Reward , Animals , Conditioning, Classical/physiology , Dose-Response Relationship, Drug , Locomotion/drug effects , Locomotion/physiology , Male , Mice , Receptors, N-Methyl-D-Aspartate/physiology
2.
J Neuroinflammation ; 12: 3, 2015 Jan 09.
Article in English | MEDLINE | ID: mdl-25573647

ABSTRACT

BACKGROUND: Lipopolysaccharide (LPS) induces neuroinflammation and memory deficit. Since polyamines improve memory in various cognitive tasks, we hypothesized that spermine administration reverses LPS-induced memory deficits in an object recognition task in mice. The involvement of the polyamine binding site at the N-methyl-D-aspartate (NMDA) receptor and cytokine production in the promnesic effect of spermine were investigated. METHODS: Adult male mice were injected with LPS (250 µg/kg, intraperitoneally) and spermine (0.3 to 1 mg/kg, intraperitoneally) or ifenprodil (0.3 to 10 mg/kg, intraperitoneally), or both, and their memory function was evaluated using a novel object recognition task. In addition, cortical and hippocampal cytokines levels were measured by ELISA four hours after LPS injection. RESULTS: Spermine increased but ifenprodil decreased the recognition index in the novel object recognition task. Spermine, at doses that did not alter memory (0.3 mg/kg, intraperitoneally), reversed the cognitive impairment induced by LPS. Ifenprodil (0.3 mg/kg, intraperitoneally) reversed the protective effect of spermine against LPS-induced memory deficits. However, spermine failed to reverse the LPS-induced increase of cortical and hippocampal cytokine levels. CONCLUSIONS: Spermine protects against LPS-induced memory deficits in mice by a mechanism that involves GluN2B receptors.


Subject(s)
Memory Disorders/chemically induced , Memory Disorders/drug therapy , Spermine/therapeutic use , Analysis of Variance , Animals , Cytokines/metabolism , Discrimination, Psychological/drug effects , Disease Models, Animal , Dose-Response Relationship, Drug , Enzyme-Linked Immunosorbent Assay , Excitatory Amino Acid Antagonists/pharmacology , Exploratory Behavior/drug effects , Lipopolysaccharides/toxicity , Male , Mice , Piperidines/pharmacology , Recognition, Psychology/drug effects
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