European Neuropsychopharmacology
Volume 22, Issue 6 , Pages 424-430, June 2012

VEGF regulates antidepressant effects of lamotrigine

  • Rongju Sun

      Affiliations

    • Department of Emergency, General Hospital of PLA, Beijing 100853, China
    • ,
  • Nanxin Li

      Affiliations

    • Department of Psychology, Yale University, New Haven, CT 06520, USA
    • Corresponding Author InformationCorrespondence to: N. Li, Department of Psychology, Yale University, New Haven, CT 06520, USA. Tel.: +1 203 8156200.
    • ,
  • Tanshi Li

      Affiliations

    • Department of Emergency, General Hospital of PLA, Beijing 100853, China
    • Corresponding Author InformationCorrespondence to: T. Li, Department of Emergency, General Hospital of PLA, Beijing 100853, China. Tel.: +86 10 66936224.

Received 18 July 2011; received in revised form 29 August 2011; accepted 29 September 2011. published online 28 October 2011.

Abstract 

The anticonvulsant drug lamotrigine has been shown to produce strong antidepressant effects in the treatment of bipolar disorder patients. Our previous studies have demonstrated that brain derived neurotrophic factor (BDNF) signaling plays an important role in regulating its behavioral actions in several rodent models of depression. The current study extends earlier work on BDNF and explores the role of another important neurotrophin vascular endothelial growth factor (VEGF) in regulating the antidepressant actions of lamotrigine. The results showed that chronic administration of 30mg/kg lamotrigine (14days) normalized the down-regulated frontal and hippocampal VEGF protein expression as well as the behavioral deficits induced by chronic unpredictable stress. In addition, pharmacological inhibition of VEGF signaling by infusion of SU5416, a selective Flk-1 receptor inhibitor, blocks the antidepressant effects of lamotrigine in all behavioral paradigms. Taken together, this study provides further evidence that VEGF is also an essential regulator for the antidepressant effects of lamotrigine.

Keywords: Antidepressant, VEGF, CUS, FST, Lamotrigine, NSF

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PII: S0924-977X(11)00263-X

doi:10.1016/j.euroneuro.2011.09.010

European Neuropsychopharmacology
Volume 22, Issue 6 , Pages 424-430, June 2012

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