Benefits of agomelatine in behavioral, neurochemical and blood brain barrier alterations in prenatal valproic acid induced autism spectrum disorder.
Valproic acid administration during gestational period causes behavior and biochemical deficits similar to those observed in humans with autism spectrum disorder. Although worldwide prevalence of autism spectrum disorder has been increased continuously, therapeutic agents to ameliorate the social impairment are very limited. The present study has been structured to investigate the therapeutic potential of melatonin receptor agonist, agomelatine in prenatal valproic acid (Pre-VPA) induced autism spectrum disorder in animals. Pre-VPA has produced reduction in social interaction (three chamber social behavior apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complex I, II, IV). Furthermore, Pre-VPA has increased locomotor activity (actophotometer), anxiety, brain oxidative stress (thiobarbituric acid reactive species, glutathione, and catalase), nitrosative stress (nitrite/nitrate), inflammation (brain and ileum myeloperoxidase activity), calcium levels and blood brain barrier leakage in animals. Treatment with agomelatine has significantly attenuated Pre-VPA induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, agomelatine also attenuated Pre-VPA induced increase in locomotion, anxiety, brain oxidative stress, nitrosative stress, inflammation, calcium levels and blood brain barrier leakage. It is concluded that, Pre-VPA has induced autism spectrum disorder, which was attenuated by agomelatine. Agomelatine has shown ameliorative effect on behavioral, neurochemical and blood brain barrier alteration in Pre-VPA exposed animals. Thus melatonin receptor agonists may provide beneficial therapeutic strategy for managing autism spectrum disorder.
CNS Research Lab, Department of Pharmacology, School of Pharmacy, Bharat Institute of Technology, Partapur Bypass, Meerut, Uttar Pradesh, India. Electronic address: sharmaslab7@gmail.com.
Hariom
H
Kumar
School of Pharmacy, Bharat Institute of Technology, Partapur Bypass, Meerut, Uttar Pradesh, India. Electronic address: sharmaslab1@gmail.com.
B M
BM
Sharma
Amity Institute of Pharmacy, Amity University, Sector-125, Noida, Uttar Pradesh, India; CNS Pharmacology, Conscience Research, Pocket F-233, B, Dilshad Garden, Delhi 110095, India. Electronic address: conscienceresearch@scientist.com.
Bhupesh
B
Sharma
D000081:Acetamides / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants; D000067877:Autism Spectrum Disorder / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects; D007398:Interpersonal Relations; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D014635:Valproic Acid; D009281:Naphthalenes
D000081:Acetamides; D000927:Anticonvulsants; D018696:Neuroprotective Agents; D012701:Serotonin; D014635:Valproic Acid; C084711:agomelatine; D009281:Naphthalenes
Calcium; Intestinal motility; Melatonin receptor agonists; Mitochondrial function; Neurodevelopment; Serotonin