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 pre-treated 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.
Joca
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Department of Pharmacology, Laboratory of Physiology and Pharmacology of the Central Nervous System, Centro Politécnico, Setor de Ciências Biológicas, Universidade Federal do Paraná, P.O. Box 19031, PR, 81 540-970, Curitiba, Brazil.
Skalisz
L L
LL
Beijamini
V
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Vital
M A
MA
Andreatini
R
R
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001058:Apomorphine; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use*; D002375:Catalepsy / Q000139:chemically induced / Q000188:drug therapy; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000627:therapeutic use; D006220:Haloperidol; D008297:Male; D018377:Neurotransmitter Agents; D000078330:Oxcarbazepine; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D019956:Stereotypic Movement Disorder / Q000139:chemically induced / Q000188:drug therapy; D013550:Swimming / Q000523:psychology
D000928:Antidepressive Agents; D018492:Dopamine Antagonists; D018377:Neurotransmitter Agents; D011954:Receptors, Dopamine; D002220:Carbamazepine; D006220:Haloperidol; D001058:Apomorphine; D000078330:Oxcarbazepine