Figure 8

Schematic of signaling pathways involved in methamphetamine-induced astrocyte activation via positive-feedback loop of σ-1R expression. Exposure of astrocytes to methamphetamine leads to activation of astrocytes via up-regulation of σ-1R. Inhibition of σ-1R, Src, or ERK MAPKs resulted in the subsequent inactivation of the downstream CREB transcription factor. CREB binds to the promoter of σ-1R, leading to enhanced σ-1R expression with subsequent astrocyte activation, thereby amplifying the methamphetamine response.