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Increased oxidative stress in submitochondrial particles after chronic amphetamine exposure
Benício N Frey1, Samira S Valvassori, Karin M Gomes
1Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil.
Brain Research
|May 30, 2006
Summary
Chronic amphetamine exposure increases mitochondrial reactive oxygen species (ROS) production in rat brains, suggesting a potential model for studying neuropsychiatric disorders like bipolar disorder and schizophrenia.
Area of Science:
- Neuroscience
- Biochemistry
- Pharmacology
Background:
- Reactive oxygen species (ROS) are implicated in neuropsychiatric disorders.
- Mitochondrial dysfunction is increasingly linked to bipolar disorder (BD) and schizophrenia (SCZ).
Purpose of the Study:
- To investigate the effects of acute and chronic d-amphetamine administration on ROS production in rat brain mitochondria.
- To explore the potential of amphetamine-induced mitochondrial oxidative stress as a model for BD and SCZ pathophysiology.
Main Methods:
- Male Wistar rats received acute or chronic d-amphetamine injections.
- Locomotor activity was assessed using the open field task.
- Thiobarbituric acid reactive substances (TBARS) and superoxide production were measured in brain submitochondrial particles.
Main Results:
- Both acute and chronic d-amphetamine increased locomotor activity.
- Chronic, but not acute, d-amphetamine significantly elevated TBARS and superoxide production in the prefrontal cortex and hippocampus.
- A 3- to 6-fold increase in TBARS and a 1.5- to 2-fold increase in superoxide were observed after chronic treatment.
Conclusions:
- Chronic amphetamine exposure induces mitochondrial oxidative stress in rat brain regions relevant to neuropsychiatric disorders.
- This model may be valuable for investigating altered brain energy metabolism in BD and SCZ.
- Further research is needed to evaluate interventions like mood stabilizers and antipsychotics in mitigating this oxidative stress.
