Carisbamate and lamotrigine are anticonvulsants which act on neuronal voltage-gated sodium channels. Carisbamate has been shown to have antidepressant-like effects in animal models of depression, and lamotrigine is a mood stabilizer with a therapeutic effect in depressive episodes of patients with bipolar disorder. This study examined the effects of carisbamate and lamotrigine on monoaminergic transmission in rodents which could contribute to their antidepressant action. In vivo electrophysiological recordings were carried out in rats, after 2 and 14 days administration of vehicle, carisbamate (60 mg/kg/day) or lamotrigine (25 mg/kg/day). Overall firing activity of the dorsal raphe nucleus (DRN) serotonin (5-HT), locus coeruleus (LC) norepinephrine (NE) and ventral tegmental area (VTA) dopamine (DA) neurons were decreased with carisbamate. Lamotrigine also decreased 5-HT neuronal firing and this effect was dampened by lesion of the prefrontal cortex. Despite these decreases in firing activity after their prolonged administration, both anticonvulsants exhibited significant increase in tonic activation of hippocampus 5-HT1A receptors as shown by a disinhibition of the firing activity of pyramidal neurons in response to the selective antagonist WAY-100635. This reveals an increase in 5-HT level that may be attributed to a desensitization of the terminal 5-HT1B autoreceptors. This study demonstrates that sustained carisbamate and lamotrigine administration decreases 5-HT firing in the DRN but nevertheless enhances 5-HT transmission in the forebrain. This serotonergic effect may be associated with an antiglutamatergic action, and may contribute to the antidepressant-like effect of carisbamate in the forced swim test (FST) and the antidepressant properties of lamotrigine.
- The American Society for Pharmacology and Experimental Therapeutics