Administration of a cAMP phosphodiesterase 4 inhibitor enhances antidepressant-induction of BDNF mRNA in rat hippocampus

The influence of two selective phosphodiesterase 4 (PDE4) inhibitors, rolip ram and Ro 20-1724, on the induction of BDNF mRNA by antidepressant treatme nt was examined. Coadministration of rolipram or Ro 20-1724 with an antidep ressant (either desipramine or Org 4428) for 21 d resulted in a significant induction of BDNF mRNA in hippocampus relative to administration of vehicl e. Coadministration of a PDE4 inhibitor with an antidepressant for 7 or 14 d also increased levels of BDNF mRNA. In contrast, acute coadministration d id not influence levels of BDNF mRNA. In situ hybridization analysis demons trated that the induction of BDNF mRNA in response to the repeated coadmini stration paradigm occurs in the dentate gyrus granule and CA1 and CA3 pyram idal cell layers of hippocampus. These findings demonstrate that coadminist ration shortens the time required for the upregulation of BDNF mRNA, suppor ting the possibility that this treatment may provide an effective therapy f or major depression. [Neuropsychopharmacology 22:42-51, 2000] (C) 1999 Amer ican College of Neuropsychopharmacology. Published by Elsevier Science Inc.