The antipsychotic olanzapine reduces memory deficits and neuronal abnormalities in a male rat model of Autism

• Published in: Journal of chemical neuroanatomy Vol. 132; p. 102317
• Main Authors: Lima-Castañeda, Luis Ángel, Bringas, María Elena, Aguilar-Hernandez, Leonardo, Garcés-Ramírez, Linda, Morales-Medina, Julio César, Flores, Gonzalo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-10-2023
• Subjects: Autism spectrum disorder; Hippocampus; Morris water maze; Nitric oxide; Novel object recognition test; Olanzapine; Valproic acid; Morris water maze; Novel object recognition test; Olanzapine; Nitric oxide; Valproic acid; Autism spectrum disorder; Hippocampus
• ISSN: 0891-0618; 1873-6300; 1873-6300
• DOI: 10.1016/j.jchemneu.2023.102317

The prevalence of autism spectrum disorder (ASD), a neurodevelopmental condition that impacts social interaction and sensory processing, is rising. Valproic acid (VPA) exposure during pregnancy causes autistic-like traits in offspring. Olanzapine (OLZ), an atypical antipsychotic, is used to treat ASD. We assessed the impact of OLZ on behavior, neuromorphology, and nitric oxide (NO) levels in the hippocampus using prenatal VPA treatment in rats. It is commonly known that ASD patients exhibit sensory abnormalities. As such, we utilized the tail flick test to validate the ASD model. In the novel object recognition test (NORT), VPA exposure reduces the discrimination index (DI) in the first introduction to the novel object. Moreover, OLZ and vehicle-treated rats perform differently in the second exposition to the DI of the novel object, suggesting that OLZ reverses VPA-induced deficits in recognition memory. The latency to find the hidden platform in the Morris water maze test of memory and learning improves in VPA-exposed rats after OLZ administration, indicating that OLZ improves spatial memory in these rats. Administration of prenatal VPA induces neuronal hypotrophy and reduces spine density in pyramidal neurons of the CA1 region of the hippocampus. Treatment with OLZ corrects the neuromorphological changes brought on by VPA. In the CA1 region of the hippocampus, VPA treatment increases the number of neurons, which normalizes with OLZ treatment. OLZ increases the NO levels in the dorsal hippocampus in control rats. In rats exposed to VPA, the second-generation antipsychotic OLZ reduces memory-related and neuroplastic alterations. The current findings support the use of OLZ in this illness and further validate the use of prenatal VPA as a model of ASD.
•Valproic acid (VPA) exposure during pregnancy is a model of autism spectrum disorder (ASD) in rodents.•Olanzapine (OLZ), an atypical antipsychotic, is used to treat ASD at present time.•VPA exposure induces recognition and spatial memory in male rats.•VPA exposure induces neuronal hypotrophy and a reduction in spine density in the hippocampus.•OLZ treatment ameliorates the behavioral and neuronal deficits observed in VPA exposed rats.