First author: Cunha-Oliveira, Teresa (poster)
Poster board C96 - Mon 05/07/2010, 13:30 - Hall 1
Session 108 - Mental disorders 3
Abstract n° 108.13
Publication ref.: FENS Abstr., vol.5, 108.13, 2010
||Cunha-Oliveira T. (1), Rego A. C. (1, 2), Garrido J. (3), Borges F. (4), Macedo T. (5) & Oliveira C. R. (1, 2)
||(1) Center for Neuroscience and Cell Biology, Coimbra, Portugal; (2) Inst. Biochemistry, Fac. Medicine, Univ. Coimbra, Coimbra, Portugal; (3) CIQUP, Chem. Eng. Dep., Sch. Eng., ISEP, Porto, Portugal; (4) CIQUP, Dep. Chem, Fac. Sci., Univ. Porto, Porto, Portugal; (5) AIBILI, Coimbra, Portugal
||Neurotoxicity of sequential and simultaneous exposure to heroin and cocaine in rat cortical neurons
||Cocaine and heroin are frequently co-abused by humans, in a combination known as speedball. Previously, we showed that cocaine or heroin exposure induces apoptotic hallmarks in cortical neurons. Moreover, chemical interactions between heroin (Her) or its metabolite morphine and cocaine (Coc) were recently described to occur in heroin-cocaine mixtures, resulting in the formation of strong adducts. Taking this into account, we evaluated whether combinations of Coc and Her affect the neurotoxicity of these drugs, using rat cortical neurons incubated with Coc, Her, Her followed by Coc (Her+Coc) and Her:Coc added simultaneously (1:1). Neurons exposed to Her, Her+Coc and Her:Coc exhibited a decrease in cell viability, which was more pronounced in neurons exposed to Her and Her+Coc, in comparison with neurons exposed to the mixture (Her:Coc). Cells exposed to this mixture showed increased intracellular calcium and mitochondrial dysfunction, as determined by a decrease in intracellular ATP levels and in mitochondrial membrane potential, displaying both apoptotic and necrotic characteristics. Conversely, a major increase in cytochrome c release, caspase-3-dependent apoptosis, and decreased metabolic neuronal viability were observed upon sequential exposure to Her and Coc. The data show that drug combinations potentiate cortical neurotoxicity and that the mode of co-exposure alters cellular death pathways activated by the drugs, strongly suggesting that chemical interactions occurring in Her:Coc, such as adduct formation, shift cell death mechanisms towards necrosis. Since impairment of the prefrontal cortex is involved in the loss of impulse control observed in drug addicts, our data may contribute to explain the increase in treatment failure observed in speedball abusers.
Supported by University of Coimbra (III/34/2008) and FCT-Portugal (POCI/SAU-FCF/58330/2004 and SFRH/BPD/34711/2007).
||C - Disorders of the nervous system
Mental disorders / Addiction and drugs of abuse
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