Cocaine induces cell death and activates the transcription nuclear factor kappa-b in pc12 cells

Cocaine is a worldwide used drug and its abuse is associated with physical, psychiatric and social problems. The mechanism by which cocaine causes neurological damage is very complex and involves several neurotransmitter systems. For example, cocaine increases extracellular levels of dopamine and free radicals, and modulates several transcription factors. NF-κB is a transcription factor that regulates gene expression involved in cellular death. Our aim was to investigate the toxicity and modulation of NF-κB activity by cocaine in PC 12 cells. Treatment with cocaine (1 mM) for 24 hours induced DNA fragmentation, cellular membrane rupture and reduction of mitochondrial activity. A decrease in Bcl-2 protein and mRNA levels, and an increase in caspase 3 activity and cleavage were also observed. In addition, cocaine (after 6 hours treatment) activated the p50/p65 subunit of NF-κB complex and the pretreatment of the cells with SCH 23390, a D1 receptor antagonist, attenuated the NF-κB activation. Inhibition of NF-κB activity by using PDTC and Sodium Salicilate increased cell death caused by cocaine. These results suggest that cocaine induces cell death (apoptosis and necrosis) and activates NF-κB in PC12 cells. This activation occurs, at least partially, due to activation of D1 receptors and seems to have an anti-apoptotic effect on these cells.

This work was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (C. S.). L.B.L., C.D.M., E.M.K. are supported by student research fellowship from FAPESP and L.B.L. is also supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). L.S.L. is supported from USP and C.S., R.C. and C.S.P. are research fellow from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).

This work was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (C. S.). L.B.L., C.D.M., E.M.K. are supported by student research fellowship from FAPESP and L.B.L. is also supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). L.S.L. is supported from USP and C.S., R.C. and C.S.P. are research fellow from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).