• J Guo, P Lin, X Zhao, J Zhang, X Wei, Q Wang, and C Wang.
• Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China; Zhejiang Provincial Key Laboratory of Pathophysiology in Ningbo University School of Medicine, Ningbo, Zhejiang 315211, PR China.
• Neuroscience. 2014 Mar 28;263:1-14.

AbstractIncreasing evidence has indicated that immune challenge by bacterial lipopolysaccharide (LPS) induces depressive-like behavior, neuroinflammatory response and upregulates phosphodiesterase-4 (PDE4), an enzyme that specifically hydrolyzes cyclic adenosine monophosphate (cAMP). However, whether the potential PDE4 inhibitor etazolate prevents the LPS-induced depressive-like behavior remains unclear. Here using a model of depression induced by the repeated administration of LPS during 16days, and then investigated the influence of LPS on the expression of PDE4, interleukin-1β (IL-1β) and antidepressant action of etazolate in mice through forced swimming, novelty suppressed feeding, sucrose preference and open-field tests. Our results showed that etazolate pretreatment facilitated the recovery from weight loss and prevented the depressive-like behavior induced by repeated LPS administration. Moreover, the antidepressant action of etazolate was paralleled by significantly reducing the expression levels of PDE4A, PDE4B, PDE4D and IL-1β and up-regulating the cAMP/phosphorylated cAMP response-element binding protein (pCREB)/brain-derived neurotrophic factor (BDNF) signaling in the hippocampus and prefrontal cortex of mice. These results indicate that the effects of etazolate on the depressive-like behavior induced by repeated LPS treatment may partially depend on the inhibition of PDE4 subtypes, the activation of the cAMP/pCREB/BDNF signaling and the anti-inflammatory responses in the hippocampus and prefrontal cortex.Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

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