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Wednesday, March 23, 2011

Fluoxetine, Desipramine, and the Dual Antidepressant Milnacipran Reduce Alcohol Self-Administration and/or Relapse in Dependent Rats



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We studied the effect of the dual antidepressant milnacipran on ethanol operant self-administration in acutely withdrawn ethanol-dependent and in -non-dependent Wistar rats, and used fluoxetine and desipramine to dissect both 5-HT and NE components, respectively, in the effect of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 (1.0g/kg) conditioned place preference in control rats and ethanol-induced locomotor sensitization in DBA/2J female mice.

Milnacipran dose dependently (5–40mg/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 (10mg/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 (20mg/kg) countered sensitization development and reduced its expression at 1 week after treatment; fluoxetine (10mg/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.



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