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Chronic methylphenidate abuse: Effects on behaviour, redox homeostasis, and cholinergic system
Natália Freddo1, Jéssica Nardi2, Wagner Antonio Tamagno3
1Programa de Pós-Graduação em Bioexperimentação, Universidade de Passo Fundo, BR 285, São José, Passo Fundo, Rio Grande do Sul, Brazil.
Abstract:
Methylphenidate (MPH) (metil 2-fenil-2-(piperidin-2-il) acetato) is used as a drug of abuse as well as a cognitive enhancer owing to its amphetaminic structure. The objective of this study was to evaluate whether chronic exposure to an abusive context and dose of MPH (80 mg/L for 15 min/day for 7 days) in adult life causes behavioural changes related to anxiety, fear, sociability, locomotion, and memory as well as altered levels of biochemical markers, cortisol, and the cholinergic system. Here we used the zebrafish (Danio rerio) as a translatio Nnal model. We showed that fish exposed to MPH showed marked hypolocomotion and anxiogenic patterns, fear behaviour, and memory delay. MPH exposure also increased the levels of antioxidant enzymes, non-protein thiols, and reactive oxygen species compared with those in the control group, and the redox status was altered at the cerebral and peripheral levels. The cholinergic system exhibits a reduction in signalling and an increase in cortisol levels. Our results clarified the mechanisms involved in the toxicity elicited by the abusive use of MPH. Overall, our results demonstrated that chronic administration of an abusive dose of MPH in individuals without a diagnosis of attention deficit hyperactivity disorder (ADHD) can cause important damage.
Insights
Abusive methylphenidate (MPH) use in adults without ADHD causes anxiety, fear, and memory deficits. This drug abuse alters biochemical markers, cortisol, and the cholinergic system, leading to significant damage.
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- Methylphenidate (MPH) is misused as a cognitive enhancer due to its amphetamine-like structure.
- Understanding the neurobiological effects of chronic, high-dose MPH exposure is crucial.
Purpose of the Study:
- To investigate behavioral and biochemical alterations in zebrafish following chronic, abusive methylphenidate exposure.
- To elucidate the mechanisms underlying MPH toxicity in non-ADHD individuals.
Main Methods:
- Adult zebrafish (Danio rerio) were exposed to a high dose of MPH (80 mg/L/day for 7 days).
- Behavioral tests assessed locomotion, anxiety, fear, and memory.
- Biochemical analyses measured antioxidant enzymes, thiols, reactive oxygen species, cortisol, and cholinergic markers.
Main Results:
- MPH exposure induced hypolocomotion, anxiety-like behavior, fear responses, and memory impairment.
- Increased levels of antioxidant enzymes, non-protein thiols, and reactive oxygen species were observed.
- Reduced cholinergic signaling and elevated cortisol levels indicated neurochemical disruption.
Conclusions:
- Chronic abusive methylphenidate use causes significant behavioral and neurochemical changes.
- The study clarifies mechanisms of MPH toxicity, highlighting potential damage in individuals without ADHD.
- Findings underscore the risks associated with non-prescribed, high-dose MPH administration.
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