One binge-type cycle of alcohol plus ketamine exposure induces emotional-like disorders associated with oxidative damage in adolescent female rats

This work is supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-FINANCE CODE 001); Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq/ Brazil for her Research Productivity Grant (number 311335/2019–5 to CSFM); R.R.L. is a researcher from the CNPq, under grant number 312275/ 2021–8. Research Pro-Rectory of the Federal University of Pará (PROPESP, UFPA, Brazil).Federal University of Pará. Institute of Health Science. Faculty of Pharmacy. Laboratory of Pharmacology of Inflammation and Behavior. Belém, PA, Brazil.Federal University of Pará. Institute of Health Science. Faculty of Pharmacy. Laboratory of Pharmacology of Inflammation and Behavior. Belém, PA, Brazil.Federal University of Pará. Institute of Health Science. Faculty of Pharmacy. Laboratory of Pharmacology of Inflammation and Behavior. Belém, PA, Brazil.Federal University of Pará. Institute of Health Science. Faculty of Pharmacy. Laboratory of Pharmacology of Inflammation and Behavior. Belém, PA, Brazil.Federal University of Pará. Institute of Health Science. Faculty of Pharmacy. Laboratory of Pharmacology of Inflammation and Behavior. Belém, PA, Brazil.University of Pará State. Center for Biological and Health Sciences. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Science. Laboratory of Pharmacology and Toxicology of Cardiovascular System. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Federal University of Pará. Institute of Biological Sciences. Laboratory of Functional and Structural Biology. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Citogenômica e Mutagênese Ambiental. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Citogenômica e Mutagênese Ambiental. Ananindeua, PA, Brasil.Ophir Loyola Hospital. Laboratory of Molecular Biology. Belém, PA, Brazil.Ophir Loyola Hospital. Laboratory of Molecular Biology. Belém, PA, Brazil.Federal University of Pará. Institute of Health Science. Faculty of Pharmacy. Laboratory of Pharmacology of Inflammation and Behavior. Belém, PA, Brazil.Federal University of Pará. Institute of Health Science. Faculty of Pharmacy. Laboratory of Pharmacology of Inflammation and Behavior. Belém, PA, Brazil.Drug abuse is a global public health problem among adolescents, with alcohol often used in association with other psychotropic drugs, such as ketamine. Considering the scarcity of evidence, this study aimed to investigate emotional behavioral effects induced by ethanol plus ketamine co-abuse, as well as oxidative biochemistry, and neurotrophic mediator in the prefrontal cortex and hippocampus in the early withdrawal of adolescent female rats. Animals were divided into control, ethanol, ketamine, and ethanol plus ketamine groups. The protocol administration was performed for 3 consecutive days (binge-like pattern). Behavioral assays of open field, elevated plus maze, and forced swim test were performed. After that, the prefrontal cortex and hippocampus were collected to evaluate oxidative biochemistry (reactive oxygen species-ROS; Antioxidant capacity against peroxyl radicals-ACAP; and lipid peroxidation). We found that isolated or combined ethanol and ketamine exposure displayed anxiety- and depressive-like profile, in a non-synergistically manner during early withdrawal. However, oxidative damage was aggravated in the co-administered animals than in isolated exposed subjects. We concluded that ethanol plus ketamine co-abuse may intensify oxidative damage in the hippocampus and prefrontal cortex in the early withdrawal of adolescent female rats, which was not reflected in the emotional behavioral phenotype