Naloxone-reversible antidepressant-like effect of carbamazepine in mice: Without tolerance and withdrawal syndrome

Abstract

It has been shown that carbamazepine, an anticonvulsant drug, has antidepressant effects. Moreover, the involvement of opioid system has been shown in the pathophysiology of depression. Here, we sought to determine the possible role of the opioid system in the antidepressant-like effect of carbamazepine after acute and repeated administration. The antidepressant-like activity was assessed in the mice forced swimming test (FST). Carbamazepine (20, 30, and 40 mg/kg, i.p.) or morphine were administrated 30 min before the OFT or FST. Data showed that carbamazepine has an antidepressant effect in a dose-dependent manner which was attenuated by naloxone (1 mg/kg, i.p., a nonselective opioid receptor antagonist). ED50 values against despair behaviors were 34.75 (29.37-50.81) mg/kg and 0.34 (0.09-0.78) mg/kg for carbamazepine and morphine, respectively. Additionally, low dose of dose of carbamazepine (30 mg/kg) induced a synergistic effect in the FST with low dose of morphine (0.1 mg/kg) that was antagonized by naloxone. Furthermore, in contrast to morphine, carbamazepine after repeated administration induced neither tolerance to the antidepressant-like effect nor withdrawal syndrome. The results demonstrated that carbamazepine exerted an antidepressant-like effect possibly through the opioidergic pathway, without inducing tolerance and withdrawal signs.