Effects of desipramine on rat behavior are prevented by concomitant treatment with ethanol.
Ethanol prevents the decrease of the number of beta-adrenoceptors in the cerebral cortex induced by chronic treatment of rats with desipramine. The activation of the adenylate cyclase, the second messenger, by beta-adrenergic agonists is reduced somewhat less than after treatment with desipramine alone. The present paper examined the hypothesis that ethanol inhibits the neuronal adaptation to desipramine chronic treatment at the functional level as well. Desipramine reduced exploratory behavior (crossings, rearings) as did ethanol. Combined treatment attenuated the effect of desipramine. Cognitive performance 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 beta-adrenergic mechanisms was assessed by injection of salbutamol, a beta-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 treatment. However, rats treated with desipramine were less active than those treated with tap water or ethanol. The effect of desipramine in the presence of a high concentration of salbutamol was attenuated by ethanol. The observed increase of the number of wet dog shakes correlates with the function of these receptors. In two paradigms, spontaneous motility and apomorphine-induced hypothermia, ethanol did not affect 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 by chronic treatment with the antidepressant desipramine. This is of special interest since the adaptation of beta-adrenoceptors is thought to be critical for the antidepressant efficacy of various therapeutic interventions applied in psychiatric practice.
Rommelspacher
H
H
Department of Neuropsychopharmacology, Free University, Berlin, F.R. Germany.
Wolffgramm
J
J
Widjaja
S
S
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002540:Cerebral Cortex / Q000201:enzymology / Q000378:metabolism; D003891:Desipramine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism
D011943:Receptors, Adrenergic, beta; D000431:Ethanol; D006916:5-Hydroxytryptophan; D000262:Adenylyl Cyclases; D001058:Apomorphine; D000420:Albuterol; D003891:Desipramine