Role of selective 5-HT2C ligands on maternal separation induced ultrasonic vocalization and c-fos expression in paternal duplicated mouse pups

Background: Autism and Autism spectrum disorders (ASD) are neurodevelopmental psychiatric disorders characterized by impairments of language, communication, social interaction, stereotype and repetitive behavior.Qualitative impairments in communication such as abnormal language and poor interactive communication skills are fundamental to the diagnosis of autism.Chromosome-engineered Paternal duplicated mouse (PatD/+) pups showed some characteristic features of autism including abnormal USVs at developmental postnatal age when compared with wild type mouse pups.Objective: To study the effect of an selective 5-HT 2C R agonist (WAY161503) on USVs production in paternal duplicated pups and area of brain involve on it Methods: On the day of experiment pups were kept into the home cage with their dam and transported into the experimental room; left undisturbed for 1 hour.Pups were injected (IP) either with drug or vehicle and put back into the home cage.Thirty minutes later each pup was placed on a metal plate inside the sound proof chamber, where temperature was maintained at 24°C by circulating water through a reservoir below the plate.Ultrasonic sound produced by the pups was recorded for 5 minutes.Genotyping was performed to determine the Paternal duplicated and wild type pups.Quantitative measurement of C-fos was done at different brain region by immunohistochemistry. C-fos is extensively used as a marker of neural activation in brain.Results: At 1 mg/kg 5HT 2C receptor agonist showed changes in USVs in wild type pups compared to vehicle (33±22 vs116±87, P≤ 0.001.No significant difference was observed in case of antagonist ((110±74 vs 70± 26, P= 0.058).No significant difference was observed in alteration of USVs in paternal duplicated pups compared to vehicle group in response to agonist and antagonist (194±114 vs 249±122, P=0.22; 74±62 vs 88±75, P =0.49 respectively).At retroambiguus nucleus brain region, c-fos expression was significantly expressed in paternal duplicated pups compared with wild type. Conclusion:Reduced USVs in response to 5-HT 2C R agonist & increased neuronal activation of retroambiguus (NRA) brain region in paternal duplicated pups reflects the involvement of 5-HT 2C R and its phenotypes relevant to the treatment symptoms of autism.