Fabomotizole corrects behavioral impairments in a postnatal propionic acid model of autism spectrum disorders in rats
Abstract
Background. Postnatal administration of propionic acid (PPA) to rats during the period of active neural network maturation models persistent behavioral disorders characteristic of autism spectrum disorders (ASD). Fabomotizole, which has a multifactorial mechanism of action (sigma-1 receptor activation, modulation of GABAergic and glutamatergic transmission), may have a corrective effect on these disorders. Objective. To study the effect of fabomotizole on behavioral disorders in Wistar rats with an ASD model induced by postnatal PPA administration. Methods. ASD was modeled in male Wistar rats by subcutaneous injections of PPA at a dose of 500 mg/kg on postnatal days 21–25 (P21–P25). Fabomotizole (10 mg/kg) was administered orally daily from P26 until the end of the experiment. Between P52 and P85, social behavior (Pair Test), stereotypy (Autogrooming), anxiety (Open Field Test, Elevated Plus Maze), exploratory activity (Hole Board Test), cognitive functions (Y-maze), and response to aversive odor were assessed. Results. Postnatal PPA administration caused persistent impairments: social deficit (4.3-fold decrease in communicative acts, 26-fold increase in aggression), stereotypy (6.4-fold increase in grooming duration), anxiety (4.4-fold decrease in time spent in open arms), cognitive deficit (2.2-fold decrease in Y-maze patrolling efficiency), and disrupted species-specific behavior. Fabomotizole corrected the PPA-induced impairments: normalized social behavior (4.6-fold increase in communicative acts, 10.5-fold decrease in aggression), reduced stereotypy (5.5-fold decrease in grooming duration), exerted an anxiolytic effect (8.5-fold increase in time spent in open arms), and improved cognitive functions (2.7-fold increase in patrolling efficiency). Conclusion. Fabomotizole at a dose of 10 mg/kg with long-term oral administration attenuates the main behavioral disorders in rats with the postnatal PPAinduced ASD model, confirming its therapeutic potential against persistent symptoms of autism spectrum disorder.