Julia Zaccarelli-Magalhães1, André Rinaldi Fukushima2, Natalia Moreira2, Marianna Manes2, Gabriel Ramos de Abreu2, Esther Lopes Ricci3,4, Paula A Faria Waziry5, Helenice de Souza Spinosa2. 1. Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, Av. Prof. Dr. Orlando Marques de Paiva, 87, São Paulo, 05508-270, Brazil. julia.zaccarelli@usp.br. 2. Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, Av. Prof. Dr. Orlando Marques de Paiva, 87, São Paulo, 05508-270, Brazil. 3. Health Science Institute, Presbiterian Mackenzie University, Rua Da Consolação, 930, São Paulo, 01302-907, Brazil. 4. School of Health Science IGESP, Rua da Consolação, 1025, São Paulo, 01301-000, Brazil. 5. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, 3200 S. University Drive, Fort Lauderdale, FL, 33328, USA.
Abstract
BACKGROUND: Depression is one of the most common mentally debilitating diseases in the world. Ketamine has been recently identified as a potential novel antidepressant. Further animal model evaluations of the use of ketamine as an antidepressant are necessary to determine safety parameters for clinical use. Therefore, the objective of this study was to perform toxicological tests of prolonged treatment using three different doses of ketamine in adult male rats. METHODS: The animals were divided into four groups: three treated with 5, 10 or 20 mg/kg of ketamine and a control group treated with saline solution. Intraperitoneal route of treatment was administered daily for 3 weeks. Body weight, water and food intake were measured once a week, as well as evaluation of the functional observational battery, which includes methodic monitoring of motor activity, motor coordination, behavioral changes, and sensory/motor reflex responses. Upon completion of treatment period, all animals were euthanized by decapitation followed by immediate collection of samples, which included brain structures and blood for neurochemical, hematological and biochemical analyses. RESULTS: Rats treated with the highest tested dosage (20 mg/kg) of ketamine had lower weight gain in the 1st and 2nd weeks of treatment and all experimental groups had measurable alterations in the serotoninergic system. CONCLUSIONS: Our data indicate that the alterations observed are minor and due to a predicted mechanism of action, which implies that ketamine is a promising drug for repurposing as an antidepressant.
BACKGROUND:Depression is one of the most common mentally debilitating diseases in the world. Ketamine has been recently identified as a potential novel antidepressant. Further animal model evaluations of the use of ketamine as an antidepressant are necessary to determine safety parameters for clinical use. Therefore, the objective of this study was to perform toxicological tests of prolonged treatment using three different doses of ketamine in adult male rats. METHODS: The animals were divided into four groups: three treated with 5, 10 or 20 mg/kg of ketamine and a control group treated with saline solution. Intraperitoneal route of treatment was administered daily for 3 weeks. Body weight, water and food intake were measured once a week, as well as evaluation of the functional observational battery, which includes methodic monitoring of motor activity, motor coordination, behavioral changes, and sensory/motor reflex responses. Upon completion of treatment period, all animals were euthanized by decapitation followed by immediate collection of samples, which included brain structures and blood for neurochemical, hematological and biochemical analyses. RESULTS:Rats treated with the highest tested dosage (20 mg/kg) of ketamine had lower weight gain in the 1st and 2nd weeks of treatment and all experimental groups had measurable alterations in the serotoninergic system. CONCLUSIONS: Our data indicate that the alterations observed are minor and due to a predicted mechanism of action, which implies that ketamine is a promising drug for repurposing as an antidepressant.
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