PET imaging in rat brain shows opposite effects of acute and chronic alcohol exposure on phosphodiesterase-4B, an indirect biomarker of cAMP activity.

ABSTRACT: The cyclic adenosine monophosphate (cAMP) cascade is thought to play an important role in regulating alcohol-dependent behaviors, with potentially opposite effects following acute versus chronic administration. Phosphodiesterase 4 (PDE4) is the primary brain enzyme that metabolizes cAMP, thereby terminating its signal. Radioligand binding to PDE4 serves as an indirect biomarker of cAMP activity, as cAMP-protein kinase A (PKA)-mediated phosphorylation of PDE4 increases its affinity for radioligand binding ~10-fold. Of the four PDE4 subtypes, PDE4B polymorphisms are known to be strongly associated with alcohol and substance use disorders. This study imaged rats with the PDE4B-preferring positron emission tomography (PET) radioligand [¹⁸F]PF-06445974 following acute and chronic eth

SUBMITTER: Tang S 

PROVIDER: S-EPMC11632093 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature