Methylphenidate Enhances NMDA-Receptor Response in Medial Prefrontal Cortex via Sigma-1 Receptor: A Novel Mechanism for Methylphenidate Action
Figure 7
MPH enhancement of NMDA-R current is mediated via intracellular Ca2+ dependent PLC/PKC signaling pathway.
MPH produced no effect on NMDA-induced current when the PLC inhibitor U73122, the PKC inhibitor chelerythrine, the Ca2+ chelating reagent BAPTA, or the IP3 inhibitor 2-APB was administered, but still enhanced the current when the PKA inhibitor fragment 5-24 (PKI5-24) or L-type Ca2+ channel blocker nefedipine was applied. NMDA-R currents were recorded in the presence of CNQX, TTX and BMI, with holding potential of -40 mV. Shown in figure are the normalized histograms for MPH effects in the presence of U73122, chelerythrine, PKI5-24, BAPTA, nefedipine and 2-APB. *P<0.05 vs. control. **P<0.01 vs. control, paired t-test. Numbers mean the cell recorded.