title: Mitochondrial complex I dysfunction induced by cocaine and cocaine plus morphine in brain and liver mitochondria.
abstract: Mitochondrial 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.
authors.affiliation: CNC, Center for Neuroscience and Cell Biology, University of Coimbra, Largo Marquês de Pombal, 3004-517 Coimbra, Portugal. mteroliv@cnc.cj.uc.pt
authors.forename: Teresa
authors.initials: T
authors.lastname: Cunha-Oliveira
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Silva
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Silva
authors.forename: António J
authors.initials: AJ
authors.lastname: Moreno
authors.forename: Catarina R
authors.initials: CR
authors.lastname: Oliveira
authors.forename: Maria S
authors.initials: MS
authors.lastname: Santos
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D019069:Cell Respiration / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009020:Morphine; D003042:Cocaine