INHIBITION OF REINFORCING EFFECTS OF MORPHINE AND MOTIVATIONAL ASPECTS OF NALOXONE-PRECIPITATED OPIOID WITHDRAWAL BY N-METHYL-D-ASPARTATE RECEPTOR ANTAGONIST, MEMANTINE

The present study focused on the effects of 1-amino-3,5-dimethyladaman tane (memantine), a clinically used, low-affinity N-methyl-D-aspartate channel blocker, on the motivational impact of morphine and morphine withdrawal syndrome. Memantine (7.5 mg/kg) inhibited the acquisition a s well as the expression of morphine-induced conditioned place prefere nce. However, memantine did not affect significantly the acquisition o r expression of conditioned place preference induced by food presentat ion. In addition, at the dose that blocked morphine-induced conditione d place preference, memantine by itself produced neither conditioned p lace preference nor conditioned place aversion. Memantine attenuated t he negative motivational aspects of morphine withdrawal as assessed by conditioned place aversion produced by a low dose (0.1 mg/kg) of nalo xone in morphine-dependent rats. Drug discrimination studies revealed that the inhibitory effects of memantine on morphine-induced condition ed place preference could not be attributed to the attenuation by mema ntine of the interoceptive cue produced by morphine, In addition, the inhibitory effects of memantine on the expression of morphine-induced conditioned place preference seemed not to be related to effects on me mory retrieval, as revealed in the Morris water maze spatial task. The se data suggest that memantine at a low, pharmacologically relevant do se of 7.5 mg/kg blocks the reinforcing effects of morphine and aversiv e effects of morphine withdrawal in rats, which suggests a new potenti al clinical indication for this agent in the treatment of opioid abuse .