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Inhibition of methamphetamine-induced apoptosis by the calcium channel blocker verapamil in rat cerebellar neurons
Author(s): 
Pages: 361-365
Year: Issue:  4
Journal: JOURNAL OF PEKING UNIVERSITY(HEALTH SCIENCES)

Keyword:  MethamphetamineVerapamilNeurotoxinsApoptosis;
Abstract: Objective: To study protective effects of verapamil on neurotoxicity induced by methamphetamine (MA) in rat cerebellar neuronal cells (R2 cells ) and explore the possible mechanisms,Methods: MA neurotoxicity to R2 cells was examined by MTT reduction and LDH leakage assays. Using flow cytometer and agarose gel electrophoresis, apoptosis induced by MA in R2 cells was observed. The effects of verapamil on neurotoxicity and apoptosis induced by MA in R2 cells were determined. Results:(1) Incubation of the R2 cells with MA (0.25 -3.00 mmol/L) for 48 h or 60 h concentration-dependently increased the LDH content in the extra-cellular bathing medium by 48.2% - 89.3% and 62.5%-97.3%, respectively. Exposure to MA elicited the apoptotic DNA peak of the R2 cells (I. E. Sub-G1 peak) in a concentration- and time-dependent manner by the use of flow cytometer. Agarose gel electro phoresis showed a typical DNA laddering pattern.( 2 ) Verapamil ( 0.5 - 5.0 μmol/L) reduced the number of dead cells and the LDH content in the extra-cellular bathing medium, ameliorated morphological changes, and inhibited apoptosis induced by MA in R2 cells. Conclusion: These results suggest that verapamil has a neuroprotective effect on MA-induced apoptosis, and that L-type voltage dependent calcium channel may be involved in the neurotoxitic effect of MA.
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