The antidepressive-like effect of oxcarbazepine: possible role of dopaminergic neurotransmission

It has been previously shown that oxcarbazepine (OXCBZ), a keto-analogue of carbamazepine, exhibits an antidepressive-like effect profile in the learned helplessness and forced swimming test (FST). Since carbamazepine possesses dopaminergic effect, the present study was carried out to evaluate the extent to which the antidepressive effect of OXCBZ might be mediated by dopaminergic system. Thus, the effects of OXCBZ in haloperidol-induced catalepsy and apomorphine-induced stereotypy were studied. The anti-immobility effect of OXCBZ in the FST was also evaluated in haloperidol pretreated rats. OXCBZ (40 and 80 mg/kg, i.p.) dose-dependently reduced the catalepsy induced by haloperidol (2.0 mg/kg, i.p.). Moreover, OXCBZ (80 mg/kg, but not 20 or 40 mg/kg, i.p.) increased the intensity of apomorphine-induced stereotypy (0.6 mg/kg, s.c.). Finally, it was observed that the combination of OXCBZ (80 mg/kg, i.p.) and haloperidol (0.5 mg/kg, i.p.) antagonized the anti-immobility effect of OXCBZ and further increased the immobility time when compared to haloperidol alone. Haloperidol alone (0.5 or 1.0 mg/kg) did not change the immobility time. Thus, these results suggest that OXCBZ could enhance dopaminergic neurotransmission, which might mediate its antidepressive-like effect. (C) 2000 Elsevier Science B.V. All rights reserved.