Objectives: Several studies indicate that prolonged ethanol exposure enhances N-methyl-D-aspartate (NMDA) receptor-stimulated nitric oxide (NO) formation, which may play an important role in alcohol dependence, withdrawal, and
alcohol-associaed
brain damage. Acamprosate (calcium acetylhomotaurine) is a putative anti-craving drug used to maintain abstinence in alcoholics and appears to interact with NMDA receptor, a subclass of glutamate receptors. The present study was designed to
investigate
the effects of acamprosate on the expression of nitric oxide synthase (NOS) in the rat brain, following chronic ethanol exposure. NOS expression was assessed by histochemical detection of nicotinamide adenine dinucleotide phosphate
(NADPH)-diaphorase
activity.
Methods: Adult male Spraque-Dawley rats were used. They were randomly assigned to one of three groups; Ethanol with vehicle treated group(1 ㏄/㎏/i.p.), Ethanol with acamprosate treated group (400 ㎎/㎏/i.p.), and control group without
ethanol
exposure. They were given 5% ethanol for 8 weeks. The ethanol with acamprosate treated rats were given acamprosate for 4 weeks. Histochemistry for NADPH-diaphorase, a marker for neurons containing NOS, was performed.
Results:
1) In the ethanol with vehicle treated group, the number of NADPH-diaphorase-positive cells was significantly increased in the frontal cortex and dentate gyrus compared with control group.
2) In the ethanol with acamprosate treated group, the number of NADPH-diaphorase-positive cells was significantly decreased in he frontal cortex and dentate gyrus compared with ethanol with vehicle treated group.
Conclusion: The present study supports that acamproaste may attenuate ethanol-induced NMDA-mediated processes, such as NO formation and neurotoxicity. This is in keeping with the concept of acamprosate acting as NMDA receptor antagonist.
Furthermore, theses finding suggest that the possible mechnism involved in the role of nitric oxide in alcohol dependence.
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