Cyamemazine decreases ethanol intake in rats and convulsions during ethanol withdrawal syndrome in mice |
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Authors: | Mickaël Naassila Elisabeth Legrand Françoise d’Alche-Birée M Daoust |
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Institution: | Faculté de Pharmacie, 1 rue des Louvels, F-80000 Amiens, France, FR UFR de Médecine-Pharmacie de Rouen, BP 97, F-76803 Saint Etienne Rouvray Cédex, France e-mail: daoust@easynet.fr, Fax: +33-3-2282 7672, FR Rh?ne Poulenc Rorer Company, 15 rue de la Vanne, F-92120 Montrouge, France, FR
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Abstract: | The effect of cyamemazine a dopamine D2 receptor antagonist on voluntary ethanol consumption in rats and on ethanol withdrawal in mice was examined. Male Sprague-Dawley
rats were tested in a free choice (water and 10% ethanol) experiment and consumed 5 g/kg ethanol daily. Rats were treated
daily IP with cyamemazine ( 0.5, 1, or 2 mg/kg) or acamprosate (100 mg/kg) during 2 weeks. Both acamprosate and 1 mg/kg cyamemazine
significantly decreased ethanol intake by 45% without affecting either fluid or food intake. The lowest dose of cyamemazine
had no effect on alcohol intake but increased food intake. The highest dose had no effect on any variables. During the post-treatment
period, only 1 mg/kg cyamemazine decreased both ethanol and fluid intakes. Mice were made dependent on alcohol using a chocolate
fluid diet containing increasing concentrations of alcohol and withdrawn after 9 days. Mice were treated with cyamemazine
(1 or 0.5 mg/kg, respectively) or with the same doses of lorazepam acutely on the day of withdrawal or chronically (during
alcohol treatment). Both chronic and acute cyamemazine and lorazepam treatments decreased convulsions during ethanol withdrawal.
Both acute treatments decreased locomotor activity in control and alcohol dependent mice. Chronic treatment had no effect
on locomotor activity. We suggest that cyamemazine could reduce alcohol consumption by antagonizing the activation of the
dopaminergic pathways during the induction of alcohol dependence. The action of cyamemazine on 5-HT3 receptors could also explain its effect on alcohol convulsions during withdrawal convulsions.
Received: 19 October 1997/Final version: 6 April 1998 |
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Keywords: | Cyamemazine Acamprosate Lorazepam Alcohol dependence Alcohol withdrawal Dopamine |
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