Cocaine affects astrocyte iNOS expression.

Astrocytes play important roles in brain pathology. Astrocytes can express inducible nitric oxide synthase (iNOS), which is responsible for the transient production of nitric oxide (NO). Both iNOS and NO have been reported to be actively involved in cocaine addiction. We aimed to investigate if cocaine could directly affect astrocyte iNOS expression. An in vitro astrocyte culture model and an in vivo chronic cocaine mouse model were used. In the in vitro model, astrocytes from human cerebral cortex were treated with cocaine. iNOS expression was measured using solid-phase ELISA and Western blot. Changes in astrocyte morphology were quantified using a Sholl analysis. In the in vivo model, wild type C57BL/6 mice were treated with cocaine for two weeks. Mouse brain tissue, especially in the prefrontal cortex (PFC), was collected. Astrocyte number and iNOS expression were measured. The results demonstrated that cocaine could cause significant morphological changes in astrocytes in vitro. Cocaine could also cause a significant increase in astrocyte iNOS expression in vitro. The in vivo studies showed that chronic cocaine treatment significantly decreased the number of astrocytes in the mouse PFC, resulting in a decreased iNOS expression. In summary, astrocytes could directly respond to cocaine stimulation in vitro and in vivo, and iNOS was involved. Therefore, investigation into the role of astrocytes and iNOS in cocaine addiction may bring insight to new therapeutic targets for cocaine use disorder.