Neurotoxicity of Isotretinoin in Mice: Behavioral and Tissue Neurological Function Assessment

Background: Isotretinoin is used to treat some skin disorders in dogs and cats by reducing the size and activity of their sebaceous glands, although it may have some neurobehavioral side effects. Objectives: To evaluate isotretinoin’s effects on the brain and neurotransmitters, as well as its impact on neurobehavior and motor activity. Methods: Fifteen mice were divided into three groups: the first group was a control group, the second group received 125 mg/kg isotretinoin, and the third group received 250 mg/kg orally. Results: The LD50 for isotretinoin is 4841.2 mg/kg. Neurobehavioral measurements of mice revealed significant effects on changes in open-field activity, time spent in dark areas, and negative geotaxis behaviors across different dosage levels of isotretinoin. Both doses of isotretinoin (125 and 250 mg/kg) significantly altered serotonin levels. Mice treated with 125 mg/kg isotretinoin exhibited a decrease in serotonin levels compared to the control group. Both doses of isotretinoin resulted in significant changes in acetylcholine levels. Isotretinoin (125 mg/kg) slightly increased in acetylcholine levels. The data indicated a significant increase in catechol-O-methyltransferase (COMT) enzyme levels. A histopathological study of the brain revealed that 125 mg/kg isotritinoin induced mild vacuolization, blood vessel congestion, and mild perivascular edema. A high dose (250 mg/kg) resulted in vacuolization, gliosis, blood vessel congestion, hemorrhage and satellitosis. Conclusion: High oral doses of isotretinoin influence animal neurobehavioral behavior due to its effect on brain tissue, as evidenced by its effects on serotonin, acetylcholine and the COMT enzyme.