Insufficient sleep compromises the cAMP signaling pathway in the hippocampus, negatively impacting hippocampus-dependent memory. In the current study, we explored whether selective PDE4B or selective PDE4D inhibition can improve hippocampus-dependent spatial memory in the object location test (OLT) in mice after sleep deprivation (SD). The results demonstrated that SD impaired the OLT performance, and both A-33 and zatolmilast protected against the negative consequences of SD when administered at the start and middle of the SD period. These findings suggest that both PDE4B and PDE4D subfamilies contribute to the beneficial effect of PDE4 inhibition against SD-induced memory consolidation impairment.
© 2025 Zhao et al.; Published by Cold Spring Harbor Laboratory Press.
