Niti Sharma, Bhupesh Sharma*, Neerupma Dhiman and Lalit K. Golani
Background: Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with complex aetiology and phenotypes. Maternal consumption of alcohol is known to produce deleterious effects in the progeny, generating ADHD related phenotypes. Phosphodiesterase-3 (PDE3) has been shown to provide benefits in various brain conditions.
Objective: To investigate the role of a selective PDE3 inhibitor, effects of cilostazol administration on core phenotypes of prenatal alcohol exposure (PAE) model of ADHD were assessed.
Methods: PAE was established by exposing animals to 6/4 g.kg-1 (weekdays/weekends) ethyl alcohol from gestational day 8-20 and cilostazol (30/60 mg.kg-1 p.o.) was administered to the offspring (PND21-48) of females exposed to ethyl alcohol. To identify probable mechanisms involved, the effects on 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. Also, effects on behaviour such as hyperactivity, inattention and anxiety were assessed.
Result: PAE induced hyper-locomotion, inattention, and anxiety in tested animals. Administration of cilostazol to PAE group of animals resulted in amelioration of behavioural deficits. Also, cilostazol resulted in a significant increase in the levels of BDNF, pCREB, IL-10 and GSH along with significant decrease in TNF-α, IL-6 and TBARS in different brain areas of PAE group.
Conclusion: Cilostazol, a selective PDE3 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.
ADHD, PDE3, cilostazol, prenatal-alcohol, neuro-inflammation, oxidative stress.
Department of Pharmacology, Amity Institute of Pharmacy, Amity University Uttar Pradesh, Noida, , Department of Pharmacology, Amity Institute of Pharmacy, Amity University Uttar Pradesh, Noida, , Amity Institute of Pharmacy, Amity University Uttar Pradesh, Noida, , Department of Chemistry and biochemistry, Milwaukee institute of drug discovery, University of Wisconsin, Milwaukee