The mood stabilizer lamotrigine produces antidepressant behavioral effects in rats: role of brain-derived neurotrophic factor

The anticonvulsant drug lamotrigine has been shown to produce strong antidepressant effects in the treatment of patients with bipolar disorder. However, to date there are few preclinical reports on its behavioral actions in animal models of depression or its underlying molecular mechanisms. The current study investigated the effects of lamotrigine in the forced swimming test and the learned helplessness test. The results demonstrate that both 15 and 30 mg/kg acute treatment of lamotrigine significantly reduced immobility in the forced swimming test without affecting locomotor activity. Sub-chronic twice daily injections of 30 mg/kg lamotrigine robustly decreased escape failures in animals that had developed learned helplessness symptoms. In parallel, the sub-chronic lamotrigine treatment also up-regulated frontal and hippocampal brain-derived neurotrophic factor expression in both naive and stressed animals and restored the stress-induced down-regulation of brain-derived neurotrophic factor expression. This study provides further evidence for the use of lamotrigine as a novel antidepressant in the treatment of bipolar disorders.