Autor(es):
Teresa Cunha-Oliveira 
; A. Cristina Rego ; Jorge Garrido ; Fernanda Borges ; Tice Macedo ; Catarina R. Oliveira
Data: 2010
Identificador Persistente: http://hdl.handle.net/10216/54029
Origem: Repositório Aberto da Universidade do Porto
Assunto(s): Ciências da Saúde; Neurociências; Neuroquímica, Ciências Físicas; Química; Química aplicada
Descrição
Cocaine and heroin are frequently co-abused by humans, in a combination known as speedball. Recently,
chemical interactions between heroin (Her) or its metabolite morphine (Mor) and cocaine (Coc) were
described, resulting in the formation of strong adducts. In this work, 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 plus Coc (Her:Coc, 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 the 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 changes
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, the data presented
here may contribute to explain the increase in treatment failure observed in speedball abusers.
