Effects of desipramine of rat behavior are prevented by concomitant treatment with ethanol

Abstract

Ethanol prevents the decease of the number of β-adrenoceptors in the cerebral cortex induced by chronic treatment of rats with desipramine. The activation of the adenylate cyclase, the second messenger, by β-adrenergic agonists is reduced somewhat less than after treatment with desipramine alone. The present paper examined the hypothesis that ethanol inhibits the neuronal adaption to desipramine chronic treatment at the fucntional level as well. Desipramine reduced exploratory behavior (crossings, rearings) as did ethanol. Combined treatment attnenuate the effect of desipramine. Cognitive performace was investigated using an active avoidance paradigm. Desipramine-treated rats did not learn the task in contrast to control animals. Again, combination treatment with ethanol improved the ability of the rats to perform the task. The activity of cerebral β-adrenergic mechanisms was assessed by injection of sulbutamol, a β-adrenoceptor agonist in rats pretreated with 5-hydroxytryptophan (5-HTP). The augmentation of the 5-HTP-induced wet dog shake behavior by salbutamol was observed in all animals independent of the chronic treament. However, rat treated with desipramine were less active than those treated with tap water or ethanol. The effect of desipramine of a high concentration of salbutamol was attnuated by ethanol. The observed increased of the number of wet dog shakes correlates with the funtion of these receptors. In two paradigms, spontaneous motility and apomorphine-induced hypothermia, ethanol did not effect the action of desipramine. It is noteworthy that desipramine acted in both situations within a short time period (minutes to hours). The findings strongly suggest that ethanol can prevent adaptive changes in the brain induced in the brain by chronic treatment with the antidepressant desipramine. This is of special interest since the adaption of β-adrenoceptors is thought to be critical for the antidepressant efficacy of cvarious therapeutic interventions applied in psychiatric practice.