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                <forename type="first">Mickaël</forename>
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            <funder>This study was supported by the Regional Council of Picardie (RCP), INSERM, MiLDT/Inca/INSERM, Institut de France/Fondation NRJ, and IREB. ES and HH are supported by doctoral fellowships from the RCP; RL is supported by a doctoral fellowship from MENRT. SA is supported by a post-doctoral fellowship from the RCP.</funder>
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                  <biblScope unit="issue">7</biblScope>
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                  <date type="datePub">2011-06</date>
                  <date type="dateEpub">2011-03-23</date>
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                <term xml:lang="fr">comportement</term>
                <term xml:lang="fr">opérante</term>
                <term xml:lang="fr">auto-administration</term>
                <term xml:lang="fr">rat</term>
                <term xml:lang="fr">rechute</term>
                <term xml:lang="fr">locomotion</term>
                <term xml:lang="fr">sensibilisation</term>
                <term xml:lang="fr">transporteur</term>
                <term xml:lang="fr">milnacipran</term>
                <term xml:lang="fr">désipramine</term>
                <term xml:lang="fr">fluoxétine</term>
                <term xml:lang="fr">sérotonine</term>
                <term xml:lang="fr">dépendance</term>
                <term xml:lang="fr">inhaltion</term>
                <term xml:lang="fr">addiction</term>
                <term xml:lang="fr">alcoolisme</term>
                <term xml:lang="fr">alcool</term>
              </keywords>
              <classCode scheme="mesh">Alcoholism</classCode>
              <classCode scheme="mesh">Analysis of Variance</classCode>
              <classCode scheme="mesh">Ethanol</classCode>
              <classCode scheme="mesh">Extinction, Psychological</classCode>
              <classCode scheme="mesh">Female</classCode>
              <classCode scheme="mesh">Fluoxetine</classCode>
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              <classCode scheme="mesh">Mice</classCode>
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              <p>A few clinical studies have shown that dual antidepressants (serotonergic (5-HT) and noradrenergic (NE) transporter inhibitors, SNRIs) may be effective in alcoholism treatment. We studied the effect of the dual antidepressant milnacipran on ethanol operant self-administration in acutely withdrawn ethanol-dependent and in -non-dependent Wistar rats, and used fluoxetine and desipramine to dissect both 5-HT and NE components, respectively, in the effect of milnacipran. Milnacipran was also tested for relapse after protracted abstinence and on ethanol-induced (1.0 g/kg) conditioned place preference in control rats and ethanol-induced locomotor sensitization in DBA/2J female mice. Milnacipran dose dependently (5-40 mg/kg) attenuated the increased ethanol self-administration observed during early withdrawal and was more potent in preventing reinstatement in dependent rats after protracted abstinence as compared with non-dependent rats. Desipramine and fluoxetine (10 mg/kg) blocked ethanol self-administration during early withdrawal, and recovery was delayed in dependent animals, indicating a potent effect. Ethanol self-administration was also reduced 1 day after treatment with desipramine and fluoxetine but not with milnacipran. Finally, milnacipran prevented ethanol-induced place preference in ethanol-naive rats and reduced the magnitude of ethanol-induced sensitization associated with a delayed induction in mice. Desipramine (20 mg/kg) countered sensitization development and reduced its expression at 1 week after treatment; fluoxetine (10 mg/kg) reduced sensitization expression. Thus, 5-HT and NE transmissions during sensitization expression may mediate the effect of milnacipran on sensitization induction. These results support that SNRIs may have a potential use in alcoholism treatment.</p>
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