Effects of chronic cocaine in rat C6 astroglial cells.
Investigations with astroglial cells carry equal importance as those with neurons in drug abuse studies. The present study was aimed to investigate the effect of chronic cocaine administration on cell viability, nitric oxide (NO) production, general respiratory status of mitochondria and total protein levels in rat astroglioma cells after 24 h of treatment. In addition, the effect of cocaine was assessed for 24 h on brine shrimp larvae in order to study their sensitivity to the drug. It was observed that cocaine caused a significant dose-dependent decrease in astroglial cell viability with an LC(50) of 4.717 mM. It was found that cocaine did not induce or inhibit NO production in the cells. Evaluation of mitochondrial dehydrogenase activity in terms of formazan production in astroglial cells indicated that cocaine significantly interfered with the general respiratory status of mitochondria with an ED(50) of 6.153 mM. Furthermore, cocaine was shown to deplete the total protein levels in the cells with an ED(50) of 5.435 mM. In vivo study with brine shrimp larvae showed that these larvae were highly sensitive to cocaine with an ED(50) of 2.41 mM. In summary, our findings suggest that cocaine-induced cytotoxicity in the cells was non-specific. The cumulative effect arising from the significant loss of respiration and total cellular proteins is the cause of astroglial cell death.
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA.
Ramesh B
RB
Badisa
Carl B
CB
Goodman
D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D002460:Cell Line; D019069:Cell Respiration / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D051381:Rats
D009569:Nitric Oxide; D003042:Cocaine