LONG-TERM EXPOSURE TO SEROTONIN RECEPTOR ANTAGONISTS ALTER THE EXPRESSION OF THE N-METHYL-D-ASPARTATE RECEPTOR IN THE PRIMARY CORTICAL NEURONAL CULTURES

Objectives: To determine whether longterm suppression of the activity of serotonin receptor by non-selective or selective serotonin receptor antagonist would affect the expression of NMDA receptor in the rat primary cortical cell culture.

Methods: Rat primary cortical cell cultures were incubated with 1 ìM of non-selective 5-HT receptor antagonist, methysergide maleate or dihydroergocristine mesylate, or 1 ìM 5-HT1 selective antagonists, pindolol, or 5-HT2 selective antagonist, cyproheptadine hydrochloride, for 9 days since the third days after cells were plated. We then examined the expression of NMDA receptor in these cortical cells.

Results: Immunoblotting assay showed that the expression of NMDA receptor subunit protein NR1A and NR2A, but not the NR2B, were significant decreased after cells was long-term incubated with dihydroergocristine mesylate.

Conclusion: Long-term suppression of 5-HT receptor, probably the 5-HT1 and 5-HT2 receptor, could result into a subunit-specific down-regulation of NMDA receptor, which may alter the NMDA receptor-mediated neurotransmission in developing neuronal system in both quantitative and qualitative manner.