Ethanol and NMDA Receptor Interactions: Implications for Pharmacotherapeutic Treatments

Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China
Journal of Medical Sciences 01/2010; 30(1).


Alcohol abuse and dependence constitutes a signicant societal and global burden; however, the basic scientic knowl-edge underlying the development and maintenance of alcohol dependence is limited, resulting in few pharmacotherapies and high rates of relapse following abstinence. A growing body of evidence supports an interaction between ethanol (EtOH) and N-methyl-D-aspartate receptors (NMDARs) in mediating the acute and chronic effects of EtOH. The aim of this review is to synthesize the current knowledge of this interaction on the molecular, cellular and behavioral levels and highlight possible avenues for pharmacotherapeutic treatments.

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    ABSTRACT: In this contribution we review the biochemical pathways of ethanol and its metabolites in humans in the context of pregnancy. Special emphasis is devoted to the implications for fetal and neonatal development. The review covers primary direct effects of ethanol as well as downstream effector pathways involving modulation of receptor and hormonal signaling, and the enzymatic status of the offspring. Special attention is given to the implications of maternal alcohol consumption for the nutritional status of compounds with recognized relevance for pregnancies, such as folate, unsaturated fatty acids and zinc. The field of ethanol induced developmental disorders is enormous and still growing rapidly. Since pre-2000 material has been well covered by excellent review publications already, our manuscript concentrates on the more recent exciting developments in the field, like the interference of ethanol with neurosteroid and neuropeptide signaling. Accordingly, the references are biased heavily towards publications from the last decade. The emphasis is firmly on the biochemical pathways behind the manifestations of maternal alcohol in the neural development, physiological regulation and the immune competence of the fetus and the neonate. Extensive attention is given to the relatively new concept of in utero programming of fetal development. The epidemiological, social, or economic aspects of alcohol consumption during pregnancy are not covered by this review, as they are reviewed in other chapters of this volume
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    ABSTRACT: This study investigated the effects of ketamine on fluoxetine -induced antidepressant behaviour using the forced swimming test (FST) in mice. In order to understand the possible role of N-Methyl-D-Aspartate (NMDA) neurotransmission in the antidepressant effect of fluoxetine, different groups of mice (n=10) were administered with acute ketamine (3mg/kg, i.p.), acute NMDA (75mg/kg and 150mg/kg, i.p.) and a 21-day chronic ketamine (15mg/kg, i.p./day) were administered prior to the administration of fluoxetine (20mg/kg, i.p.) in the mice. Antidepressant related behaviour (immobility score) was measured using the forced swimming test. The results showed that the acute ketamine and fluoxetine alone treatments elicited a significant (p<0.05) reduction in immobility score compared with saline control. Furthermore, pre-treatment with acute ketamine significantly enhanced by the fluoxetine-induced decrease in immobility score. In contrast, pre-treatment with NMDA (150mg/kg) significantly (p<0.05) reversed fluoxetine -induced decrease in immobility score. On the other hand, chronic administration of ketamine significantly elicited an increase in immobility score as well as reversed the reduction induced by fluoxetine. Similarly, NMDA administration at both 75mg/kg and 150mg/kg increased immobility score in chronically administered ketamine groups. Furthermore, chronic administration of ketamine, followed by NMDA (75mg/kg) and fluoxetine significantly elevated the immobility score when compared with the group that received NMDA and fluoxetine but not chronically treated with ketamine. It can be suggested) that facilitation of NMDA transmission blocked fluoxetine-induced reduction in immobility score, while down-regulation of NMDA transmission is associated with increase in fluoxetine-induced antidepressant-related behaviour in mice. Down-regulation of the NMDA transmission is proposed as an essential component of mechanism of suppression of depression related behaviours by fluoxetine. Modulation of NMDA transmission is suggested to be relevant in the mechanism of action of fluoxetine.
    Neuroscience Letters 02/2014; 566. DOI:10.1016/j.neulet.2014.01.015 · 2.03 Impact Factor


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