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 days 8-20 and cilostazol (30/60 mg.kgsup>-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.
Results: 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 a 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.