Effects of early postnatal dopamine transporter (DAT) inhibition on social and cognitive behavior in a rat model of autism.
TL;DR
It is demonstrated that early postnatal CE-123 treatment was associated with long-lasting behavioral improvements accompanied by alterations in dopaminergic markers and BDNF expression, which support a role for dopaminergic regulation and neuroplasticity in the observed behavioral effects.
Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social behavior and cognition. Increasing evidence suggests that alterations in dopaminergic neurotransmission, including changes in dopamine transporter (DAT) function, may contribute to ASD-related behavioral abnormalities. This study investigated whether selective DAT inhibition during early postnatal development influences behavioral and molecular alterations in a rat model of ASD induced by prenatal exposure to sodium valproate (NaVP). Pregnant Wistar rats received NaVP (600mg/kg, i.p.) on gestational day 12.5. Male offspring were treated with the selective DAT inhibitor CE-123 (10mg/kg, i.p.) once daily from postnatal day (PND) 10 to 23. Behavioral assessments during adolescence (PND25-42) evaluated social interaction, recognition memory, spatial preference, anxiety-like behavior, locomotor activity, and aversive memory. DAT, dopamine D2 receptor, brain-derived neurotrophic factor (BDNF), and interleukin-1β (IL-1β) protein expression were assessed in selected brain regions. Prenatal NaVP exposure impaired social novelty discrimination, declarative, spatial, and aversive memory, reduced locomotor activity, and increased anxiety-like behavior. These behavioral alterations were accompanied by elevated DAT and dopamine D2 receptor expression. Early postnatal CE-123 treatment attenuated several ASD-like behavioral abnormalities, normalized DAT and dopamine D2 receptor expression, increased BDNF levels in the prefrontal cortex (PFC), and increased IL-1β expression, without inducing non-specific locomotor stimulation. Together, these findings demonstrate that early postnatal CE-123 treatment was associated with long-lasting behavioral improvements accompanied by alterations in dopaminergic markers and BDNF expression. Although these findings support a role for dopaminergic regulation and neuroplasticity in the observed behavioral effects, the underlying mechanisms require further investigation.