Mitochondrial dysfunction and caspase activation in rat cortical neurons treated with cocaine or amphetamine

• Type: Article in International Scientific Journal
• Date: 2006

Authors

Cunha-Oliveira, Teresa R. (Author) Other; Rego, A. Cristina (Author) Other; Cardoso, Sandra Morais (Author) Other; Borges, Fernanda Fernanda M (Author) FFUP; Swerdlow, Russell Howard (Author) Other; Macedo, Tice Reis A (Author) Other; de Oliveira, Catarina Resende (Author) Other

Journal

Title: Brain Research

Vol. 1089

Pages: 44-54

ISSN: 0006-8993

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 97 Citations

Scopus - 109 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

CORDIS: Physical sciences > Chemistry > Applied chemistry

Other information

Authenticus ID: P-004-KR2

DOI: 10.1016/j.brainres.2006.03.061

Abstract (EN): Drug abuse is associated with brain dysfunction and neurodegeneration, and various recreational drugs induce apoptotic cell death. This study examined the role of the mitochondrial apoptotic pathway in psychostimulant-induced neuronal dysfunction. Using primary neuronal cultures, we observed that amphetamine (IC50 = 1.40 mM) was more potent than cocaine (IC50 = 4.30 mM) in inducing cell toxicity. Apoptotic cell death was further evaluated using cocaine and amphetamine concentrations that moderately decreased cell reduction capacity but did not affect plasma membrane integrity. Compared to cocaine, amphetamine highly decreased the mitochondrial membrane potential, as determined using the fluorescent probe rhodamine-123, whereas both drugs decreased mitochondrial cytochrome c. In contrast to amphetamine, cocaine cytotoxicity was partly mediated through effects on the electron transport chain, since cocaine toxicity was ameliorated in mitochondrial DNA-depleted cells lacking mitochondrially encoded electron transport chain subunits. Cocaine and amphetamine induced activation of caspases-2, -3 and -9 but did not affect activity of caspases-6 or -8. In addition, amphetamine, but not cocaine, was associated with the appearance of evident nuclear apoptotic morphology. These events were not accompanied by differences in the release of the apoptosis-inducing factor (AIF) from mitochondria. Our results demonstrate that although both amphetamine and cocaine activate the mitochondrial apoptotic pathway in cortical neurons, amphetamine is more likely to promote apoptosis. (c) 2006 Elsevier B.V. All rights reserved.

Language: English

Type (Professor's evaluation): Scientific