A Comprehensive View of the Neurotoxicity Mechanisms of Cocaine and Ethanol

Abstract

Substance use disorder is an emerging problem concerning to human health, causing severe side effects, including neurotoxicity. The use of illegal drugs and the misuse of prescription or over-the-counter drugs are growing in this century, being one of the major public health problems. Ethanol and cocaine are one of the most frequently used drugs and, according to the National Institute on Drug Abuse, their concurrent consumption is one of the major causes for emergency hospital room visits. These molecules act in the brain through different mechanisms, altering the nervous system function. Researchers have focused the attention not just in the mechanism of action of these drugs, but also in the mechanism by which they damage the nervous tissue (neurotoxicity). Therefore, the goal of the present review is to provide a global perspective about the mechanisms of the neurotoxicity of cocaine and ethanol.

White matter alterations in cocaine users are negatively related to the number of additionally (ab)used substances

“…However, the use of different types of substances within a short period of time, especially cocaine and alcohol may also lead to more severe neurotoxic effects (Pereira et al . ). In addition, polysubstance users are at elevated risk of poor treatment outcome (Connor et al .…”

“…The mechanism by which cocaine may cause neural damage is suggested to be complex and seems to involve interactions with several neurotransmitter systems and modulation of transcription factors (Pereira et al . ). Recent diffusion tensor imaging (DTI) studies have demonstrated cortical white matter (WM) alterations in cocaine users (Lim et al .…”

Transplantation of human retinal pigment epithelial cells in the nucleus accumbens of cocaine self-administering rats provides protection from seeking

“…Neurosurgical interventions like DBS and GDNF replenishment into the NAc have been tried successfully in rat models of cocaine addiction (Airavaara et al, 2011; Girard et al, 2006; Green-Sadan et al, 2003; Green-Sadan et al, 2005; Lu et al, 2009; Pickens et al, 2011; Vassoler et al, 2013). Moreover, there is growing consensus that the neurobiological basis for drug addiction is becoming more clear and interventions that correct this pathophysiology may have tangible clinical benefits (Benarroch, 2015; Guercio et al, 2015; Pereira et al, 2015; Yadid et al, 2013). …”

“…We did not directly assess levels of secreted L-dopa, growth factors or cytokines at and around the graft sites or in the VTA. We also did not evaluate the fasciculus retroflex originating in the habenula that has been implicated as the source of neurogeneration and cell loss in the VTA (Benarroch, 2015; Ellison, 1992; Pereira et al, 2015). These are drawbacks of this study.…”

“…Addiction is a major disorder in which chronic exposure to alcohol or drug results in damage of the mesolimbic dopaminergic pathway projecting from the ventral tegmenal area (VTA) to the nucleus accumbens (NAc) (Trulson et al, 1987), and this damage is thought to contribute to the signature symptom of addiction: chronic relapse (reviewed in (Feltenstein and See, 2008; Pereira et al, 2015)). Recent studies have shown that the VTA derived dopaminergic inputs into the NAc have importance to the pathophysiology of reinstatement of addictive behavior (Shen et al, 2014; Smith and Villalba, 2013; Villalba and Smith, 2013).…”