Cellular and molecular mechanisms involved in the neurotoxicity of opioid and psychostimulant drugs

Cunha‐Oliveira, Teresa; Rego, A. Cristina; Oliveira, Catarina R.

doi:10.1016/j.brainresrev.2008.03.002

Cited by 198 publications

(149 citation statements)

References 163 publications

(203 reference statements)

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“…These drugs increase the extracellular concentration of monoamines, such as dopamine, leading to increased dopamine transmission [283]. Dopamine is involved in controlling reward, cognition and movement, explaining why these drugs of abuse affect locomotion [284,285].…”

Section: Psychostimulant Drugs Of Abuse and Pdmentioning

confidence: 99%

“…Amphetamines increase extraneuronal dopamine and other monoamine levels, through a nonͲexocytotic mechanism, by directly interacting with monoaminergic cells [283,286,287]. Due to its structural similarity with dopamine, amphetamine is a substrate for the DAT [288]and, when in low concentrations,itis transported by the DAT to the cytosol.…”

Section: Amphetaminesdopamine and Pdmentioning

confidence: 99%

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Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

Perfeito

Cunha‐Oliveira

Rego

2012

Free Radical Biology and Medicine

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Section: Psychostimulant Drugs Of Abuse and Pdmentioning

confidence: 99%

Section: Amphetaminesdopamine and Pdmentioning

confidence: 99%

Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

Perfeito

Cunha‐Oliveira

Rego

2012

Free Radical Biology and Medicine

Self Cite

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“…Cocaine may interact directly with mitochondria and other intracellular targets (Heard et al, 2008), after entering the cell due to its positive charge at physiological pH (Cunha-Oliveira et al, 2008). Studies in hepatic mitochondria showed that in vivo cocaine administration decreased state 3 respiration, the respiratory control ratio (RCR) and the activity of complexes I, II/III, and IV (Devi and Chan, 1997).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial complex I dysfunction induced by cocaine and cocaine plus morphine in brain and liver mitochondria

Cunha‐Oliveira

Silva

et al. 2013

Toxicology Letters

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h i g h l i g h t s• Brain and liver mitochondrial respiration is differentially affected by the drugs.• Cocaine-induced inhibition of complex I is more evident in brain mitochondria.• Dependence on complex I may explain differences in brain and liver mitochondria.• The drug combination had a greater effect on brain state 3 than the drugs per se.• In other parameters the drug combination had similar effects to cocaine per se. a r t i c l e i n f o t r a c tMitochondrial function and energy metabolism are affected in brains of human cocaine abusers. Cocaine is known to induce mitochondrial dysfunction in cardiac and hepatic tissues, but its effects on brain bioenergetics are less documented. Furthermore, the combination of cocaine and opioids (speedball) was also shown to induce mitochondrial dysfunction. In this work, we compared the effects of cocaine and/or morphine on the bioenergetics of isolated brain and liver mitochondria, to understand their specific effects in each tissue. Upon energization with complex I substrates, cocaine decreased state-3 respiration in brain (but not in liver) mitochondria and decreased uncoupled respiration and mitochondrial potential in both tissues, through a direct effect on complex I. Morphine presented only slight effects on brain and liver mitochondria, and the combination cocaine+morphine had similar effects to cocaine alone, except for a greater decrease in state-3 respiration. Brain and liver mitochondrial respirations were differentially affected, and liver mitochondria were more prone to proton leak caused by the drugs or their combination. This was possibly related with a different dependence on complex I in mitochondrial populations from these tissues. In summary, cocaine and cocaine+morphine induce mitochondrial complex I dysfunction in isolated brain and liver mitochondria, with specific effects in each tissue.

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“…Amphetamines increase extraneuronal dopamine and other monoamine levels, through a nonexocytotic mechanism, by directly interacting with monoaminergic cells [283,287,288]. Because of its structural similarity to dopamine, amphetamine is a substrate for the DAT [289] and, when in low concentrations, it is transported by the DAT to the cytosol.…”

Section: Psychostimulant Drugs Of Abuse and Pdmentioning

confidence: 99%

Reprint of: Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

Perfeito

Cunha‐Oliveira

Rego

2013

Free Radical Biology and Medicine

Self Cite

102

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a b s t r a c tParkinson disease (PD) is a chronic and progressive neurological disease associated with a loss of dopaminergic neurons. In most cases the disease is sporadic but genetically inherited cases also exist. One of the major pathological features of PD is the presence of aggregates that localize in neuronal cytoplasm as Lewy bodies, mainly composed of a-synuclein (a-syn) and ubiquitin. The selective degeneration of dopaminergic neurons suggests that dopamine itself may contribute to the neurodegenerative process in PD. Furthermore, mitochondrial dysfunction and oxidative stress constitute key pathogenic events of this disorder. Thus, in this review we give an actual perspective to classical pathways involving these two mechanisms of neurodegeneration, including the role of dopamine in sporadic and familial PD, as well as in the case of abuse of amphetamine-type drugs. Mutations in genes related to familial PD causing autosomal dominant or recessive forms may also have crucial effects on mitochondrial morphology, function, and oxidative stress. Environmental factors, such as MPTP and rotenone, have been reported to induce selective degeneration of the nigrostriatal pathways leading to a-syn-positive inclusions, possibly by inhibiting mitochondrial complex I of the respiratory chain and subsequently increasing oxidative stress. Recently, increased risk for PD was found in amphetamine users. Amphetamine drugs have effects similar to those of other environmental factors for PD, because long-term exposure to these drugs leads to dopamine depletion. Moreover, amphetamine neurotoxicity involves a-syn aggregation, mitochondrial dysfunction, and oxidative stress. Therefore, dopamine and related oxidative stress, as well as mitochondrial dysfunction, seem to be common links between PD and amphetamine neurotoxicity.

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Cellular and molecular mechanisms involved in the neurotoxicity of opioid and psychostimulant drugs

Abstract: Substance abuse and addiction are the most costly of all the neuropsychiatric disorders. In the last decades, much progress has been achieved in understanding the effects of the drugs of abuse in the brain. However, efficient treatments that prevent relapse have not been

Cited by 198 publications

References 163 publications

Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

Mitochondrial complex I dysfunction induced by cocaine and cocaine plus morphine in brain and liver mitochondria

Reprint of: Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis of Parkinson disease—resemblance to the effect of amphetamine drugs of abuse

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