Influence of prenatal exposition to valproic acid in learning process and flexibility routines in rats

Background: The comprehension of cerebral dysfunctions related to the autism spectrum disorders (ASD) is important to develop new therapeutic interventions. Animal models are among the powerful tools to address this issue. The challenge is to build a model presenting behavioral alterations in the three domains of the ASD. Today, only one model seems to fulfill this demand, the BTBR mice (McFarlane et al, 2007). The prenatal expositions to valproic acid (VPA) in rats may be an alternative to this task.

Objectives: The aim of this research was to analyze the interference of VPA in the learning process and flexibility of routines in wistar rats Methods: Pregnant females were treated by “gavage” with 800 mg/kg of VPA (SIGMA) at 9^th day of gestation (DG). The sample was composed by 20 male rats – 10 from the control group and 10 from the experimental group. The learning capacity and capacity of maintaining flexible routines are evaluated by the T maze test at 120^th post natal day (PND). At t 162^nd PND, the capacity of habituate was measured by the open field test. The learning, discrimination and reversions capacity were evaluated by the box conditioning working at 198^th PND.

Results: The results show that the VPA interfered in the capacities of learning, flexibility of routine, habituate and reversion of what is learned.

Conclusions: Prenatal exposure to VPA at 9^th DG produces alterations in the learning processes and flexibility that can be related to those described in autistic persons. In other study, the same animals showed social impairments.