Activin is a member of the
transforming growth factor-beta family that is involved in cell differentiation,
hormone secretion, and regulation of neuron survival. The cellular responses to
activin are mediated by phosphorylation of a downstream target, Smad2. The current study examines the influence of chronic electroconvulsive
seizures (ECSs), as well as chemical
antidepressants, on the expression of
activin betaA and the phosphorylation of Smad2 in the rat hippocampus and frontal cortex. Chronic ECSs (10 d) resulted in a significant increase in
activin betaA mRNA expression and Smad2 phosphorylation in both the hippocampus and frontal cortex. Chronic
fluoxetine did not influence
activin betaA expression, but
fluoxetine as well as
desipramine did increase Smad2 phosphorylation in the frontal cortex. The functional significance of increased
activin was further tested by examining the effects of
activin infusions into the hippocampus on a behavioral model of depression, the forced swim test (FST). A single bilateral infusion of
activin A or
activin B into the dentate gyrus of the hippocampus produced an
antidepressant-like effect in the FST that was comparable in magnitude with
fluoxetine. In contrast, infusion of the
activin antagonist
inhibin A did not influence behavior but blocked the effect of
activin A. The results suggest that regulation of
activin and Smad signaling may contribute to the actions of
antidepressant treatment and may represent novel targets for
antidepressant drug development.