Effects of acute and chronic treatment elicited by lamotrigine on behavior, energy metabolism, neurotrophins and signaling cascades in rats

Neurochem Int. 2011 Dec;59(8):1163-74. doi: 10.1016/j.neuint.2011.10.007. Epub 2011 Oct 25.

Abstract

The present study was aimed to investigate the behavioral and molecular effects of lamotrigine. To this aim, Wistar rats were treated with lamotrigine (10 and 20 mg/kg) or imipramine (30 mg/kg) acutely and chronically. The behavior was assessed using forced swimming test. Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), Proteina Kinase B (PKB, AKT), glycogen synthase kinase 3 (GSK-3) and B-cell lymphoma 2 (Bcl-2) levels, citrate synthase, creatine kinase and mitochondrial chain (I, II, II-III and IV) activities were assessed in the brain. The results showed that both treatments reduced the immobility time. The BDNF were increased in the prefrontal after acute treatment with lamotrigine (20 mg/kg), and the BDNF and NGF were increased in the prefrontal after chronic treatment with lamotrigine in all doses. The AKT increased and Bcl-2 and GSK-3 decreased after both treatments in all brain areas. The citrate synthase and creatine kinase increased in the amygdala after acute treatment with imipramine. Chronic treatment with imipramine and lamotrigine (10 mg/kg) increased the creatine kinase in the hippocampus. The complex I was reduced and the complex II, II-III and IV were increased, but related with treatment and brain area. In conclusion, lamotrigine exerted antidepressant-like, which can be attributed to its effects on pathways related to depression, such as neurotrophins, metabolism energy and signaling cascade.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / pharmacology*
  • Behavior, Animal / drug effects
  • Brain / drug effects*
  • Brain / metabolism
  • Brain-Derived Neurotrophic Factor / metabolism
  • Energy Metabolism / drug effects*
  • Glycogen Synthase Kinase 3 / metabolism
  • Lamotrigine
  • Male
  • Nerve Growth Factor / metabolism
  • Nerve Growth Factors / metabolism*
  • Rats
  • Rats, Wistar
  • Triazines / administration & dosage
  • Triazines / pharmacology*
  • Triazines / therapeutic use

Substances

  • Antidepressive Agents
  • Brain-Derived Neurotrophic Factor
  • Nerve Growth Factors
  • Triazines
  • Nerve Growth Factor
  • Glycogen Synthase Kinase 3
  • Lamotrigine