, 2009). Interestingly, gene expression of AKT-1 mRNA and protein, but not GSK-3β, was increased. Another study showed that sertraline potently inhibited the phosphorylation of AKT and caused cell death. (Reed, 2002). Lamotrigine has a potent activity

dependent on ion channels (i.e., Na+ and Ca+) and could have an indirect action on signal transduction (Xie and Hagan, 1998). Consistent with our results, lamotrigine had an indirect action on AKT protein levels. Whether lamotrigine has direct actions on these intracellular signaling molecules has not been extensively studied to date. To our knowledge, no other previous assay has tested such a complex mechanism. Reduced selleck compound glutamatergic neurotransmission has

been related to the antidepressant effect of lamotrigine. In fact, electrophysiological studies in the amygdala (Wang et al., 2002) and in the striatum (Calabrese et al., 1999) showed that lamotrigine reduced excitatory post-synaptic potential mediated by glutamate, an PFI-2 clinical trial effect reversed when exogenous glutamate was applied, findings consistent with the proposal that lamotrigine had an inhibitory action on glutamate release. Functional antagonists of the N-methyl-d-aspartate (NMDA) complex exhibit an antidepressant- like effect in animal models of depression. In adition, NMDA receptor antagonists have demonstrated alter neutrophins (Réus et al., 2010), and energy metabolism (Rezin et al., 2009 and Assis et al., 2009) suggesting that changes are mediated by glutamate action through NMDA receptor, thus, the effects exerted by lamotrigine in these pathways,

may be related, at least in part to its action on the glutamatergic system. In conclusion, this is the first study that directly compares the effects of acute and chronic lamotrigine treatment depressive-like symptoms together with the effects on neurotrophins, Farnesyltransferase metabolism energy, signaling cascade. The behavioral effects of lamotrigine can be attributed to its action on neurochemistry pathways related to depression. However, the results findings in the present research were in preclinical study and we suggest clinical studies evaluating serum or postmortem brain from patients with major Modulators depression and to evaluate whether lamotrigine could be a new option for this impairment disorder. This study was supported in part by grants from ‘Conselho Nacional de Desenvolvimento Científico e Tecnológico’ (CNPq-Brazil – J.Q., C.T.S. and E.L.S.), from the Instituto Cérebro e Mente (J.Q.) and UNESC (J.Q., C.T.S. and E.L.S.). J.Q. and E.L.S. are recipients of CNPq (Brazil) Productivity Fellowships. G.Z.R. is holder of a CAPES studentship. “
“The authors regret the name of one the authors was typed incorrectly. It should be Yanmin Chen, not Yanming Chen. The authors would like to apologize for any inconvenience caused.