Papaverine ameliorates prenatal alcohol-induced experimental attention deficit hyperactivity disorder by regulating neuronal function, inflammation, and oxidative stress.

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with complex aetiology and phenotypes. Phosphodiesterase-10A (PDE10A) has been shown to provide benefits in various brain conditions. We investigated the role of papaverine, a selective PDE10A inhibitor on core phenotypes in prenatal alcohol exposure (PAE) model of ADHD. In order to identify probable mechanisms involved, the effects on several protein markers of neuronal function such as, neuronal survival-BDNF, neuronal transcription factor-pCREB, brain inflammation (IL-6, IL-10 and TNF-α) and brain oxidative stress (TBARS and GSH) were studied in frontal cortex, cerebellum and striatum. PAE resulting hyper-locomotion, inattention and anxiety were studies by use of open-field, y-maze and elevated plus maze, respectively. Administration of papaverine (15/30 mg.kg-1 ) to PAE group of animals resulted in amelioration of hyperactivity, inattention, and anxiety. Also, papaverine resulted in significant increase of the levels in BDNF, pCREB, IL-10 and GSH along with significant decrease of TNF-α, IL-6 and TBARS in different brain areas of PAE group. Papaverine, a selective PDE10A inhibitor rectified behavioural phenotypes associated with ADHD, possibly by altering protein markers associated with neuronal survival, neuronal transcription factor, brain inflammation, and brain oxidative stress. Implicating PDE10A as a possible target for furthering our understanding of ADHD phenotypes.