Dopamine-1 receptor agonist, but not cocaine, modulates σ₁ gene expression in SVG cells

It has been hypothesized that σ₁ receptors (σ₁Rs) are involved in the effects of cocaine abuse. Many in vitro and in vivo studies have already indicated an influence of σ₁R ligands on dopaminergic transmission; however, the direct effect on the brain is poorly understood. Herein we describe the effects of cocaine and the selective dopamine-1 receptor (D1R) agonist, (+)-SKF38393, on gene expression of the σ₁R in a human fetal astrocyte cell line (SVG cells). This study provides the first evidence for the expression of 1RmRNAin these cells. Our results show that treatment of SVG cells with various cocaine concentrations for several time durations showed no significant alterations in 1R gene expression, as detected by real-time quantitative RT-PCR, whereas treating cells for 24 h with (+)-SKF38393 caused a significant down-regulation in σ₁ transcripts. This (+)-SKF38393-induced effect was blocked by the D1R selective antagonist (+)-SCH23390. These results suggest that the effect of cocaine on σ₁ gene expression in the brain might be indirect and mediated through D1R.