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Using Optogenetics to Reverse Neuroplasticity and Inhibit Cocaine Seeking in Rats
Published on: October 5, 2021
Chronic cocaine effects in retinal metabolism and electrophysiology: treatment with topiramate
Maria V Sánchez-Villarejo1, Rosa López-Pedrajas, Violeta Sánchez-Vallejo
1Departamento Ciencias Biomédicas, Instituto de Ciencias Biomédicas, Universidad CEU Cardenal Herrera , Moncada , Spain .
Purpose:
Cocaine abuse is a major public health problem with multiple-related complications. Indeed, cocaine can affect almost every organ of the human body, but little is known about its effects on the visual system. The main purpose of this work was to study if topiramate was able to reverse changes in retinal metabolism and retinal function induced by chronic cocaine exposure in adult rats.
Materials And Methods:
Sixteen Wistar rats were treated with a daily oral dose of cocaine during 36 days. Sixteen rats receiving NaCl 0.9% served as controls. Eight control and eight cocaine animals were administered topiramate from day 18 to day 36 of the experiment. Malondialdehyde (MDA), glutathione (GSH) and glutamate content, as well as glutathione peroxidase (GPx) activity in retina tissue homogenates were determined. Retinal function was assessed by electroretinogram (ERG).
Results:
Glutamate concentration was increased in the retinas of cocaine-treated rats. No changes in oxidative stress parameters were observed in the retinas of cocaine-treated rats when compared with the control ones. Cocaine induced a decrease in the a-wave and b-wave ERG amplitude. The administration of topiramate reversed cocaine-induced increase in glutamate concentration and had little effect on a-wave and b-wave ERG amplitude. Topiramate, a drug used during the last decade for the treatment of epileptic seizures, is able to reverse the cocaine-induced alterations observed in retinal glutamate concentration.
Conclusions:
We can conclude that retinal glutamate metabolism and function may be affected by exposure to cocaine. We confirm that topiramate, a treatment recently proposed for cocaine dependence, is also able to recover partially cocaine-induced changes in the retina.
Insights
This study shows chronic cocaine exposure alters retinal glutamate levels and function in rats. Topiramate partially reversed these cocaine-induced retinal changes, particularly glutamate concentration.
Area of Science:
- Neuroscience
- Ophthalmology
- Toxicology
Background:
- Cocaine abuse presents significant public health challenges with widespread organ complications.
- The impact of cocaine on the visual system, specifically retinal metabolism and function, remains underexplored.
Purpose of the Study:
- To investigate the potential of topiramate in reversing retinal metabolic and functional alterations caused by chronic cocaine exposure in adult rats.
- To assess topiramate's effect on retinal glutamate levels and electroretinogram (ERG) parameters following cocaine administration.
Main Methods:
- Adult Wistar rats received daily oral cocaine for 36 days, with a control group receiving NaCl 0.9%.
- Topiramate was administered to subgroups of control and cocaine-exposed rats from day 18 to day 36.
- Retinal tissue was analyzed for malondialdehyde (MDA), glutathione (GSH), glutamate, and glutathione peroxidase (GPx) activity. Retinal function was evaluated using electroretinogram (ERG).
Main Results:
- Cocaine exposure led to increased retinal glutamate concentrations and decreased ERG a-wave and b-wave amplitudes.
- No significant changes in oxidative stress markers (MDA, GSH, GPx) were observed in cocaine-treated rats compared to controls.
- Topiramate administration reversed the cocaine-induced increase in retinal glutamate but had minimal impact on ERG amplitudes.
Conclusions:
- Chronic cocaine exposure can disrupt retinal glutamate metabolism and impair retinal function.
- Topiramate demonstrates a partial recovery effect on cocaine-induced retinal changes, particularly normalizing glutamate levels.
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