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.

A novel microRNA, novel-m009C, regulates methamphetamine rewarding effects

“…injection, while SCH and RAC were intraperitoneally injected 30 min before METH injection at doses of 0.03 mg/kg and 2.0 mg/kg, respectively [ 33 , 34 ]. For conditioned place preference (CPP) test, METH (1.0 mg/kg) [ 35 ], cocaine (10.0 mg/kg) [ 36 ] and morphine (10.0 mg/kg) [ 37 ] were each intraperitoneally injected, while SPD and Arc were intraperitoneally injected 30 min before METH at doses of 30.0 mg/kg and 3.0 mg/kg respectively [ 38 ]. SKF and QNP were each intraperitoneally injected daily at doses of 5.0 mg/kg and 0.5 mg/kg respectively for repeated 7 days [ 39 , 40 ].…”

Inhibition of PSD95‐nNOS protein–protein interactions decreases morphine reward and relapse vulnerability in rats

“…Excessive production of NO is involved in several pathological forms of neural plasticity, such as opioid tolerance, dependence, and reward 1,7,8 . NMDAR antagonists such as MK‐801 attenuate these negative effects of opioids 9–12 . However, their clinical use is limited by adverse side effects (e.g., learning and memory impairment, motor ataxia, cognitive dissociation, and increased lethality) 13–17 .…”

“…1,7,8 NMDAR antagonists such as MK-801 attenuate these negative effects of opioids. [9][10][11][12] However, their clinical use is limited by adverse side effects (e.g., learning and memory impairment, motor ataxia, cognitive dissociation, and increased lethality). [13][14][15][16][17] Neuronal nitric oxide synthase (nNOS) catalytic inhibitors also suppress opioid reward, tolerance, and dependence 1,5,[18][19][20] but lack of isoform selectivity similarly contributes to unwanted side effects.…”

The effect of microinjection of CART 55-102 into the nucleus accumbens shell on morphine-induced conditioned place preference in rats: Involvement of the NMDA receptor

“…Considering the essential role of the NAc as a key structure in motivation and memory, Ahmadi and colleagues have demonstrated that systemic administration of morphine may induce passive avoidance memory through NMDA function in the NAc [33]. In another study, it was established that NMDA receptors in the NAc are involved in the reconsolidation of aversive and positive morphine-associated memories [34][35][36].…”