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Updated: Jun 19, 2026
Assessment of Cocaine-induced Behavioral Sensitization and Conditioned Place Preference in Mice
Published on: February 18, 2016
Cocaine-induced status epilepticus and death generate oxidative stress in prefrontal cortex and striatum of mice
Danielle Silveira Macêdo1, Silvânia Maria Mendes Vasconcelos, Manoel Andrade-Neto
1Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Ceará, Brazil. daniellesm2000@yahoo.com
Abstract:
Oxidative stress (OS) has been related to cocaine's actions and also to numerous nervous system pathologies, including seizures. The purpose of this work was to determine the alterations in glutathione (GSH) content, nitrite/nitrate and MDA levels after cocaine-induced toxicity. Male Swiss mice were injected (i.p.) with cocaine 90 mg/kg and observed during 1h. After this cocaine overdose some animals presented status epilepticus (SE) while some died after seizures. These animals were divided in two groups, SE and death. A group with an association of the antioxidant Vitamin E (Vit E, 400mg/kg, i.p.) plus Coc 90 (Vit E plus Coc 90) was undertaken to assess the neuroprotective effect of Vit E. Neurochemical analyses were carried out in prefrontal cortex (PFC) and striatum (ST). GSH levels increased only after cocaine-induced death in both areas studied. Cocaine-induced SE has increased nitrite/nitrate content in PFC and ST, while after death the increase was only in PFC. MDA (the lipid peroxidation marker) was elevated after SE and death in ST and only after death in PFC. Antioxidant treatment significantly reduced the GSH, nitrite/nitrate in ST and MDA levels. Only nitrite/nitrate content in PFC has not been decreased by Vit E pretreatment. The results relate that oxidative stress occurs after cocaine-induced toxicity mainly after death indicating that probably the increase of OS in the animal's brain leads to seizures and death, also showing a protective effect of Vit E in this process. Together with previous results this study contributes to the knowledge of cocaine-induced toxicity and possible in the near future to the use of antioxidants in the prevention of cocaine-induced CNS toxicity.
Insights
Cocaine overdose causes oxidative stress, leading to seizures and death in mice. Antioxidant Vitamin E showed a protective effect, reducing key markers of toxicity and neurodegeneration.
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- Oxidative stress is linked to cocaine's effects and nervous system disorders like seizures.
- Cocaine toxicity can lead to severe neurological outcomes, including status epilepticus and death.
Purpose of the Study:
- To investigate alterations in glutathione (GSH), nitrite/nitrate, and MDA levels following cocaine-induced toxicity.
- To evaluate the neuroprotective potential of Vitamin E against cocaine-induced neurotoxicity.
Main Methods:
- Male Swiss mice were administered a high dose of cocaine (90 mg/kg).
- Animals were categorized into status epilepticus (SE) and death groups.
- Neurochemical analyses were performed on prefrontal cortex (PFC) and striatum (ST) tissues.
- A group received Vitamin E pretreatment alongside cocaine to assess its protective effects.
Main Results:
- Cocaine-induced death elevated GSH levels in both PFC and ST.
- Status epilepticus increased nitrite/nitrate in PFC and ST; death showed an increase only in PFC.
- MDA levels, a marker of lipid peroxidation, rose in ST after SE and death, and in PFC post-death.
- Vitamin E treatment significantly reduced GSH, nitrite/nitrate in ST, and MDA levels, though PFC nitrite/nitrate remained unaffected.
Conclusions:
- Oxidative stress is a significant factor in cocaine-induced toxicity, particularly preceding death.
- Elevated oxidative stress in the brain may precipitate seizures and mortality.
- Vitamin E demonstrates neuroprotective properties against cocaine toxicity, suggesting potential therapeutic applications.
