Sensory and Motor Characterization in the Postnatal Valproate Rat Model of Autism

Abstract

Although autism is diagnosed according to three core features of social deficits, communication impairments, and repetitive or stereotyped behaviors, other behavioral features such as sensory and motor impairments are present in more than 70% of individuals with autism spectrum disorders (ASD). Exposure of rat pups to the teratogen valproate during sensitive periods of brain development has been shown to elicit behavioral features associated with autism diagnosis and has been proposed as a valid animal model of the disorder. The purpose of this study was to characterize sensory and motor performance in rats postnatally treated with valproate. Thirty-four rat pups were injected with either valproate (150 mg/kg) or saline on postnatal days 6–12. Auditory and tactile startle as well as auditory sensory gating was assessed during both the juvenile and adolescent stages of development; motor testing was conducted during late adolescence and included a sunflower seed eating task and a vermicelli handling task. Valproate-treated rats were underresponsive to auditory stimuli, showed deficits in auditory sensory gating, and demonstrated impairments in motor speed and performance. These findings suggest that postnatal valproate treatment elicits sensory and motor features often seen in individuals with ASD. Further, the hyposensitivity seen in postnatally valproate-treated rats contrasted with hypersensitivity previously reported in prenatally valproate-exposed rats. This suggests that timing of teratogenic exposure during early brain development may be important to consider when investigating the neurobiological basis of sensorimotor impairments in ASD.

Pre- and Neonatal Exposure to Lipopolysaccharide or the Enteric Metabolite, Propionic Acid, Alters Development and Behavior in Adolescent Rats in a Sexually Dimorphic Manner

“…Male pups were heavier and female pups were lighter than control pups, with the effects in males reaching significance across days. PPA administered in the first week of life and postnatal VPA in prior studies had no effect on body weight [23], [41]. However, while postnatal LPS has been demonstrated to not influence body weight in the first 3 weeks of life, there is some evidence of increasing body weight in males throughout adolescence [42], [43].…”

Valproic Acid Exposure during Early Postnatal Gliogenesis Leads to Autistic-like Behaviors in Rats

“…Based on behavioral criteria to diagnose ASD, such as persistent social communication and interaction deficit, and consistent results on prenatal VPA exposure animal model, we suggest that our new postnatal VPA exposure animal model also be an animal model of ASD. Interestingly, administration of VPA not only on PND 2 to 4 but also on PND 14 elicits increased locomotor activity in a novel environment, decreased social behavior, increased anxiety in an elevated plus maze, retardation in water maze performance 10,27,28). Furthermore, administration of VPA at PND 14 induces sensitivity to pain, and loss of motor skill development 29).…”

Sensory processing in autism spectrum disorders and Fragile X syndrome—From the clinic to animal models

“…It also reduces PPI in young rodents, and to a lesser extent in adult rodents, while startle response amplitudes seem to be unchanged (Schneider and Przewlocki, 2005; Schneider et al, 2006). Postnatal treatment with 150 mg/kg VPA for six days reduces startle responses and impairs PPI in adult rats as well (Reynolds et al, 2012). Interestingly, offspring of a male rat of advanced paternal age (another risk factor for ASD identified in humans; Sandin et al, 2015) has also shown to reduce startle reactivity and impair PPI (Milekic et al, 2015).…”