Effect of melatonin on behavioral features of Wistar rats with an autism spectrum disorder model induced by prenatal propionic acid administration

Background. Autism spectrum disorder (ASD) is a heterogeneous group of neurodevelopmental disorders characterized by deficits in social interaction, stereotyped behavior, and comorbid conditions (anxiety, cognitive impairments, and others). Prenatal administration of propionic acid (PPA) reproduces a complex of ASD like behavioral changes in rats. Melatonin has antioxidant, anti inflammatory and mitochondria protective effects, making it a promising candidate for the correction of these disorders.
Objective. To study the effect of melatonin on behavioral impairments in male Wistar rats in a model of ASD induced by prenatal PPA administration.
Methods. PPA was administered subcutaneously at a dose of 500 mg/kg to female rats on gestation days 12–16. The offspring were divided into the following groups: control, PPA, and PPA + melatonin. Melatonin (3 mg/kg) or distilled water was administered orally from postnatal day 6 to 70. Rat behavior was assessed in tests: Open Field, Elevated Plus Maze, Y maze, Paired test, Hole board test, Autogrooming, Three chamber social test, and Novel Object Recognition.
Results. PPA exposed rats showed reduced sociability and exploratory activity, increased anxiety, stereotypy and aggression, and cognitive impairment. Melatonin significantly corrected these impairments: it increased communicative behavior by 3.1 times and decreased aggressive manifestations by 3.7 times in the Paired test; increased the duration of contact with a social object by 4.8 times and the social preference coefficient by 2.1 times; decreased grooming duration by 2.1–3.2 times; reduced anxiety (a 13 fold increase in the number of entries into the center of the open field); improved cognitive performance in the Y maze (a 2.6 fold increase in patrolling efficiency) and in the Novel Object Recognition (an increase in preference for the novel object by 2.1 times in the number of approaches and by 5.2 times in the time spent in the arm containing it).
Conclusion. Melatonin at a dose of 3 mg/kg with long term oral administration attenuates the main and comorbid behavioral impairments in male rats with the prenatal PPA induced ASD model, substantiating its further study as a pharmacological correction agent.

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