2005 - Reinstatement of Morphine-Conditioned Reward is Blocked by Memantine
Piotr Popik1, Malgorzata Wrobel1 and Adam Bisaga2
1Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland
2New York State Psychiatric Institute at Columbia University, New York, NY, USA
Correspondence: Dr P Popik, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Kraków, Poland. Tel: +48 12 66 23 375; Fax: +48 12 637 45 00; E-mail: nfpopik@cyf-kr.edu.pl
Received: 20 December 2004
Revised: 28 March 2005
Accepted: 30 March 2005
ABSTRACT
Protection of abstinent individuals from relapse is the main goal of drug dependence treatment. Relapse is frequently precipitated by exposure to small doses of the drug of abuse or exposure to the environment that was previously associated with the drug. Mice exposed to morphine (10 mg/kg) in a unique test-box environment display a conditioned place preference for this environment. Such preference can be extinguished by subsequent pairing of physiological saline administration with the same environment. Once extinguished, the original place preference can be reinstated after a priming dose (1-2.5 mg/kg) of morphine is given. However, mice treated with 7.5 (but not 3.75) mg/kg of memantine (the glutamate/NMDA receptor antagonist) during the extinction phase were insensitive to morphine's ability to reinstate the place preference 2 days after extinction conditionings. Effect of memantine was also observed when priming dose of morphine was given 21 days after extinction conditionings. In contrast, morphine's ability to reinstate conditioned response was not affected by treatment with 10 mg/kg of chlordiazepoxide, 0.5 mg/kg of LSD-25, or 1 mg/kg of morphine given during extinction conditionings. A separate experiment demonstrated that memantine (7.5 mg/kg) treatment did not affect learning.
We show for the first time that memantine treatment during extinction conditionings may abolish the ability of drug-related cues to evoke reinstatement, suggesting that this NMDA receptor antagonist can be useful in preventing relapse in opioid dependent individuals.
Keywords: NMDA receptor antagonist; opiate; reward; reinstatement; conditioned place preference
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