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      From Ethanol to Salsolinol: Role of Ethanol Metabolites in the Effects of Ethanol

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          Abstract

          In spite of the global reputation of ethanol as the psychopharmacologically active ingredient of alcoholic drinks, the neurobiological basis of the central effects of ethanol still presents some dark sides due to a number of unanswered questions related to both its precise mechanism of action and its metabolism. Accordingly, ethanol represents the interesting example of a compound whose actions cannot be explained as simply due to the involvement of a single receptor/neurotransmitter, a scenario further complicated by the robust evidence that two main metabolites, acetaldehyde and salsolinol, exert many effects similar to those of their parent compound. The present review recapitulates, in a perspective manner, the major and most recent advances that in the last decades boosted a significant growth in the understanding on the role of ethanol metabolism, in particular, in the neurobiological basis of its central effects.

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          Most cited references108

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          Diagnostic and statistical manual of mental disorders.

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            Low doses of ethanol activate dopaminergic neurons in the ventral tegmental area.

            In unanesthetized rats the intravenous administration of low doses of ethanol (0.125-0.5 g/kg) produced a dose-dependent increase (30-80%) in the firing rate of dopaminergic (DA) neurons in the Ventral Tegmental Area (VTA). In agreement with previous observations, a dose range between 0.5 and 2 g/mg of ethanol was needed to produce comparable stimulant responses in DA neurons of the Substantia Nigra Pars Compacta. However, in anesthetized rats, doses of ethanol up to 1 g/kg failed to activate VTA-DA neurons. The high sensitivity of VTA-DA neurons to ethanol activation suggests that they might be involved in the reinforcing properties of the drug.
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              ERK2: a logical AND gate critical for drug-induced plasticity?

              Drug addiction results in part from the distortion of dopamine-controlled plasticity, and extracellular signal-regulated kinase (ERK) plays an important role in the underlying molecular mechanisms of this process. ERK is activated by drugs of abuse in a subset of neurons in reward-related brain regions. This activation, necessary for the expression of immediate early genes, depends upon dopamine D1 and glutamate receptors. Blockade of ERK activation prevents long-lasting behavioral changes, including psychomotor sensitization and conditioned place preference. It also interferes with drug craving and drug-associated memory reconsolidation. By contrast, ERK1 mutation enhances the effects of morphine and cocaine. We suggest that the ERK2 pathway acts as a logical AND gate, permissive for plasticity, in neurons on which dopamine-mediated reward signals and glutamate-mediated contextual information converge.
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                Author and article information

                Journal
                J Exp Neurosci
                J Exp Neurosci
                Journal of Experimental Neuroscience
                Journal of Experimental Neuroscience
                Libertas Academica
                1179-0695
                2016
                20 November 2016
                : 10
                : 137-146
                Affiliations
                [1 ]Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy.
                [2 ]Department of Life and Environmental Sciences, University of Cagliari, Cagliari, Italy.
                [3 ]Centre of Excellence on Neurobiology of Addiction, University of Cagliari, Cagliari, Italy.
                Author notes
                CORRESPONDENCE: acquas@ 123456unica.it
                Article
                jen-10-2016-137
                10.4137/JEN.S25099
                5117487
                807e3a5a-d9e8-43e7-82b2-502f5bc94c25
                © 2016 the author(s), publisher and licensee Libertas Academica Ltd.

                This is an open-access article distributed under the terms of the Creative Commons CC-BY-NC 3.0 License.

                History
                : 15 August 2016
                : 13 October 2016
                : 03 November 2016
                Categories
                Review

                ethanol,acetaldehyde,salsolinol
                ethanol, acetaldehyde, salsolinol

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