Antidepressant Effect of Ethaverine / 대한정신약물학회지

ABSTRACT

The effects of a L-type calcium channel blocker, ethaverine were investigated in the rat forced swimming test, after single and repeated administration. Ethaverine in doses of 20 mg/kg, 40 mg/kg after single and repeated administration reduced significantly the duration of immobility in the forced swimming test. Fluoxetine administered in a single dose of 40 mg/kg did not influence the duration of immobility, but fluoxetine in a dose of 40 mg/kg administered repeatedly reduced significantly the duration of immobility. Ethaverine in a dose of 10 mg/kg did not affect the immobility after single and repeated administration. Imipramine and fluoxetine in doses which were not effective by themselves, increased the immobilityreducing effect when administered concormitantly with ethaverine in a dose of 10 mg/kg. Imipramine in a dose of 20 mg/kg and fluoxetine in a dose of 80 mg/kg, administered alone reduced the immobility time. The reduction of immobility after the concormitant administration of ethaverine in a dose of 10 mg/kg and imipramine in a dose of 20 mg/kg, fluoxetine in a dose of 80 mg/kg was significantly greater than after imipramine or fluoxetine, administered alone. The anti-immobility effect of the ethaverine was significantly counteracted by haloperidol in a dose of 0.5 mg/kg. The effects of ethaverine on the levels of monoamines and their metabolites were also investigated in rat striatum, cerebral cortex, cerebellum, medulla oblongata, hypothalamus, midbrain, hippocampus. Treatment with ethaverine caused alterations on the levels of dopamine and its metabolite in rat striatum, cerebral cortex, hypothalamus, medulla oblongata, cerebellum, but not on the levels of norepinephrine and serotonin and its metabolite. The observed effects of ethaverine indicate that ethaverine may have an antidepressant activity and may interact with the brain dopaminergic system. The present results suggest that the concormitant administration of ethaverine and antidepressants may have a more potent therapeutic antidepressant effect and/or may permit reduction of the dose of antidepressant and thus diminish its side effects.