Abstract
Chronic cocaine use has been shown to lead to neurotoxicity in rodents and humans, being associated with high morbidity and mortality rates. However, recreational use, which may lead to addictive behavior, is often neglected. This occurs, in part, due to the belief that exposure to low doses of cocaine comes with no brain damage risk. Cocaine addicts have shown glucose metabolism changes related to dopamine brain activity and reduced volume of striatal gray matter. This work aims to evaluate the morphological brain changes underlying metabolic and locomotor behavioral outcome, in response to a single low dose of cocaine in a pre-clinical study. In this context, a Balb-c mouse model has been chosen, and animals were injected with a single dose of cocaine (0.5 mg/kg). Control animals were injected with saline. A behavioral test, positron emission tomography (PET) imaging, and anatomopathological studies were conducted with this low dose of cocaine, to study functional, metabolic, and morphological brain changes, respectively. Animals exposed to this cocaine dose showed similar open field activity and brain metabolic activity as compared with controls. However, histological analysis showed alterations in the prefrontal cortex and hippocampus of mice exposed to cocaine. For the first time, it has been demonstrated that a single low dose of cocaine, which can cause no locomotor behavioral and brain metabolic changes, can induce structural damage. These brain changes must always be considered regardless of the dosage used. It is essential to alert the population even against the consumption of low doses of cocaine.
Highlights
Drug dependency is considered a physical and psychological condition that induces chronic and recurrent diseases
The evaluation of the positron emission tomography (PET) data (SUV) showed no significant differences between the groups for any of the analyzed brain structures, which are typically affected by cocaine (Figure 4)
There is a robust body of literature regarding acute high doses of cocaine, as well as cocaine addiction scenarios, an integrated analysis of behavioral, metabolic, and structural brain changes associated with an acute low dose of cocaine is lacking
Summary
Drug dependency is considered a physical and psychological condition that induces chronic and recurrent diseases. The continued use of psychoactive substances can cause functional changes in the brain (Dias et al, 2008). Cocaine is one of the most widely used drugs in the world. The European Drug Report of 2020 showed that about 4.3 million people between 15 and 64 years old used cocaine in 2018, and 17.9 million had used it at least once (European Drug Report, 2020). In 2016, the number of young people who have already had any contact with illicit drugs was 236,800 (European Drug Report, 2016). Its consumption reaches about 0.4% of the world population, and most users (70%) are concentrated in the American continent (Gootenberg, 2019)
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