Interference of psychopharmacological agents with substance P-induced gene expression and expression of the receptor for substance P

The neuropeptide substance P (SP) has been hypothesized to be involved in the etiopathology of affective disorders. This hypothesis is based on the findings that SP-receptor antagonists have antidepressant effects in depressed patients and that SP may worsen mood. In this study, we investigated the effect of different psychopharmacological agents including antidepressants, neuroleptics, and mood stabilizing agents on SP-induced expression of interleukin-6 and expression of the SP-receptor in human astrocytoma cells. We found that the mood stabilizer valproic acid (VPA) dose-dependently inhibited SP-induced IL-6 synthesis via inhibition of protein kinase C epsilon activation. Furthermore, VPA as well as imipramine and haloperidol downregulated the expression of the substance P receptor (neurokinin(NK)-1-receptor) as assessed by real time PCR and Western blotting. Whether both mechanisms contribute to the clinical effectiveness of these substances has to be evaluated in further studies.