Effects of chronic antidepressant treatment on alpha 1- and alpha 2-adrenoceptors in the rat anococcygeus muscle

Abstract

The effects of a single administration (48 hours) and of chronic (14 days) treatment with tricyclic (desipramine, nortryptiline) and nontricyclic (mianserin, nomifensine) antidepressant drugs on responses of the isolated anococcygeus muscle to the alpha 2-adrenoceptor agonist xylazine (inhibition of contraction to field stimulation at 1 Hz) and to the alpha 1-adrenoceptor agonist phenylephrine (contraction of the muscle) have been studied. Of the drugs used only desipramine and nortryptiline administered chronically reduced the responsiveness of the anococcygeus muscle to phenylephrine suggesting a desensitization of postsynaptic alpha 1-adrenoceptors. Long-term but not acute administration of antidepressants resulted in significant decrease in sensitivity of presynaptic alpha 2-adrenoceptors to xylazine. These results show that the adaptative changes of alpha-adrenoceptors in the rat anococcygeus muscle following long-term administration may depend on the efficiency to inhibit the neuronal uptake and the ability to antagonize alpha 1-adrenoceptors.