Regulation of phosphodiesterase-4 (PDE4) expression in mouse brain by repeated antidepressant treatment: comparison with rolipram.

Abstract:

:Cyclic nucleotide phosphodiesterase-4 (PDE4) is a component of signaling pathways involved in the mediation of antidepressant activity. Of the four PDE4 subtypes, PDE4D appears to be of particular importance, given the finding that PDE4D-deficient mice exhibit an antidepressant-like behavioral phenotype. In mouse hippocampus and cerebral cortex, the effects of repeated treatment with the antidepressants desipramine and fluoxetine or the PDE4 inhibitor rolipram on the expression of PDE4D was compared to that of PDE4A and PDE4B, the other two subtypes expressed in the brain. Expression of PDE4D was increased by all drugs tested, with the exception of desipramine in hippocampus. By contrast, these treatments affected PDE4A and PDE4B expression differentially. In hippocampus, antidepressants increased PDE4A and decreased PDE4B, whereas ROL decreased PDE4A and did not change PDE4B. In cerebral cortex, antidepressants increased PDE4A and did not change PDE4B, whereas ROL did not change PDE4A and increased PDE4B. 3H-Rolipram binding was increased in cytosolic, but not in membrane, fractions of cerebral cortex by all drugs tested; there were no changes observed in hippocampus. Overall, the present results suggest some species-dependence of the regulation of PDE4 subtypes, based on data obtained previously using rats. They also suggest that the PDE4D subtype may be of particular importance as an antidepressant target in that it is regulated by repeated treatment with both norepinephrine and serotonin reuptake inhibitors as well as by the PDE4 inhibitor rolipram, drugs that produce antidepressant effects via different neuropharmacological mechanisms.

journal_name

Brain Res

journal_title

Brain research

authors

Dlaboga D,Hajjhussein H,O'Donnell JM

doi

10.1016/j.brainres.2006.04.032

subject

Has Abstract

pub_date

2006-06-22 00:00:00

pages

104-12

issue

1

eissn

0006-8993

issn

1872-6240

pii

S0006-8993(06)01104-8

journal_volume

1096

pub_type

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