Monoamine depletion and oxidative imbalance underlie ketamine-induced motor deficits in adolescent rats.

Ketamine has been widely used as a recreational substance by adolescents and young adults in nightclubs and raves in an acute manner, especially during the weekend. Considering the scarcity of evidence on the harmful consequences of adolescent ketamine recreational use on the central nervous system, primarily related to motor function, this study aimed to investigate the behavioral, biochemical, and neurochemical consequences on motor function induced by ketamine use, evaluating the motor cortex, cerebellum, and striatum in early abstinence. Adolescent female Wistar rats (28 days old) received ketamine by intranasal route (10 mg/kg/day) for 3 consecutive days. Twenty-four hours following the ketamine protocol, the animals were subjected to behavioral tests in the open field, inclined plane, pole, and rotarod tests. After behavioral assays, the animals were anesthetized and euthanized for the collection of the motor cortex, cerebellum, and striatum for biochemical and monoamine evaluations. We found that ketamine exposure in early adolescence induced a reduction in spontaneous locomotion, motor imbalance, and bradykinesia associated with oxidative stress and a decrease in neurotransmitter levels, particularly dopamine, norepinephrine, and serotonin in the striatal region. These results demonstrate that ketamine recreational use in a binge pattern in the early adolescence period displays a widespread motor function impairment during the first periods of withdrawal, which oxidative damage in motor areas and neurotransmitter reduction in the striatum may contribute to the behavioral alteration observed.