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

Autism and Autism spectrum disorders (ASD) are neurodevelopmental psychiatric disorders characterized by impairments of language, communication, social interaction, stereotype and repetitive behavior.1,2 Twin studies have shown that the narrow as well as broad phenotypes of ASD are strongly associated with genetic component.3 Etiology of the disease is unknown but it is thought to involve an interaction between multiple genes and environment factors. Diagnosis can be made by three years of age based on the presence or absence of specific behaviors that are used as diagnosis criteria. Evidence suggested that language disorder is associated in patient with autism. Knockout studies in mice have shown that mutation of certain type gene may cause the impairment of language in autistic patient but still neural mechanism is not known. In recent years several autistic mice model has been developed to investigate the actual cause of autism and ASD. Alteration of ultrasonic vocalization (USV) is frequently reported by using different model of autistic model mice, suggesting that altered USVs is a reminiscent of language impairment in humans.4–6 Infant mice, like the young of all mammalian species including humans, exhibit distress like reactions when they are separated from their dam and littermates.7,8 Their distress is signaled by the emission of 30-80 kHz USVs that can be heard by the dam and trigger their retrieval.9 Other neonatal rodents including rats, hamster and gerbils also emit maternal separation induced USVs.8,10 Drugs that reduce the anxiety in humans attenuate the emission of USVs in rat pups, leading to the use of these reactions as a screen for potentially anxiolytic compounds.14 Some studies have suggested the involvement of 5-HT2CR in anxiety like behaviour and mood disorder in mice.11–13