Journal
JOURNAL OF PHARMACY AND PHARMACOLOGY
Volume 73, Issue 11, Pages 1460-1469Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jpp/rgab115
Keywords
autism; valproic acid; PDE3; cilostazol; CREB; BDNF
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The study showed that cilostazol could alleviate prenatal VPA exposure-related hyperlocomotion, social interaction deficits, repetitive behavior, and anxiety, while significantly increasing biochemical markers such as BDNF, pCREB, IL-10, and GSH in the assessed brain regions.
Objectives Autism spectrum disorder (ASD) is categorized as a neurodevelopmental disorder, presenting with a variety of aetiological and phenotypical features. Inhibiting the enzyme phosphodiesterase-3 (PDE3) with cilostazol is known to produce beneficial effects in several brain disorders. The pharmacological outcome of cilostazol administration was investigated in prenatal valproic acid (VPA)-induced ASD deficits in albino Wistar rats. Methods Cilostazol was administered in two doses (30/60 mg/kg) to male rats born of females administered with VPA on gestational day 12. Behavioural assays on locomotion (open field), social interaction, repetitive behaviour (y-maze) and anxiety (elevated plus maze) were performed in all groups. Further, biochemical assessments of markers associated with neuronal function (BDNF, pCREB), inflammation (TNF-alpha, IL-6, IL-10) and oxidative stress were carried out in frontal cortex, hippocampus, striatum and cerebellum. Key findings The cilostazol regimen, attenuated prenatalVPA exposure associated hyperlocomotion, social interaction deficits, repetitive behavior, and anxiety. Further, biochemical markers such as BDNF, pCREB, IL-10 and GSH were found to be significantly increased contrary to markers such as TNF-alpha, IL-6 and TBARS in the assessed brain regions. Conclusions Cilostazol rectified core behavioural traits while producing significant changes to biochemistry in the brain, suggesting benefits of cilostazol administration in experimental models of ASD.
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