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Vol. 280, Issue 2, 854-865, 1997
Institute of Pharmacology, Polish Academy of Sciences, Sm The present study focused on the effects of
1-amino-3,5-dimethyladamantane (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 as well as the
expression of morphine-induced conditioned place preference. However,
memantine did not affect significantly the acquisition or expression of
conditioned place preference induced by food presentation. In addition,
at the dose that blocked morphine-induced conditioned place preference,
memantine by itself produced neither conditioned place preference nor
conditioned place aversion. Memantine attenuated the negative
motivational aspects of morphine withdrawal as assessed by conditioned
place aversion produced by a low dose (0.1 mg/kg) of naloxone in
morphine-dependent rats. Drug discrimination studies revealed that the
inhibitory effects of memantine on morphine-induced conditioned place
preference could not be attributed to the attenuation by memantine 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 memory
retrieval, as revealed in the Morris water maze spatial task. These
data suggest that memantine at a low, pharmacologically relevant dose
of 7.5 mg/kg blocks the reinforcing effects of morphine and aversive
effects of morphine withdrawal in rats, which suggests a new potential
clinical indication for this agent in the treatment of opioid abuse.
tna
12, 31-343 Kraków, Poland (P.P.), and the
Department of
Pharmacology, Merz+Co. GmbH & CO, Eckenheimer Landstrasse 100-104,
D-60318 Frankfurt am Main, Germany (W.D.)
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