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.