Abstract
Many toxic effects of cocaine are attributed to reactive oxygen species (ROS) generated during its metabolism. Recently, it has been suggested that the biological action of ROS is often confused with endogenously generated reactive sulfur species (RSS). The aim of this study was to evaluate the impact of cocaine on thiols and RSS in the rat liver and kidney in the drug self-administration (SA) paradigm and the cocaine yoked delivery model (YC) followed by drug abstinence with extinction training. The level of thiols as well as RSS formed during anaerobic metabolism of cysteine and sulfate were assayed. In addition, the activity of enzymes involved in RSS formation and glutathione metabolism were determined. In the liver, following direct cocaine administration (SA and YC), the RSS levels decreased, while in the kidneys, cocaine increased the RSS contents in both groups. These changes were maintained in these tissues during drug abstinence. The level of sulfates was changed by cocaine only in the liver. In the kidney, cocaine shifted cysteine metabolism towards an anaerobic pathway. Our study demonstrates for the first time the changes in cysteine metabolism and thiol levels in the liver and kidney of rats after cocaine self-administration and abstinence.
Highlights
Cocaine, an alkaloid derived from the leaves of the plant Erytroxylon coca growing in South America, is a potent psychoactive substance
The present study shows for the first time changes in Cys metabolism in the liver and kidneys of rats induced by intravenous self-administration of cocaine
Our study shows that cocaine in the self-administration model and in abstinence with extinction training affects thiol homeostasis and reactive sulfur species (RSS) formation in the peripheral tissues
Summary
An alkaloid derived from the leaves of the plant Erytroxylon coca growing in South America, is a potent psychoactive substance. It is a stimulant of the sympathetic nervous system acting by inhibition of dopamine (DA) reuptake from the extracellular space, and its transmission to brain structures is associated with pleasure. This buildup causes intense feelings of energy and pleasure [1,2]. It has been suggested that mechanisms other than those induced by reactive metabolites and ROS may contribute to the multi-organ toxicity of cocaine [1,6]
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