Effect of the deficiency of spinal PSD-95/SAP90 on the minimum alveolar anesthetic concentration of isoflurane in rats

Background: Spinal N-methyl-D-aspartate (NMDA) receptor activation has been demonstrated to play an important role in the processing of spinal nocicep tive information and in the determination of the minimum alveolar anestheti c concentration (MAC) of inhalational anesthetics. Postsynaptic density-95 (PSD-95)/synapse-associated protein-90 (SAP90), a molecular scaffolding pro tein that binds and clusters the NMDA receptor perferentially at synapses, was implicated in NMDA-induced thermal hyperalgesia. The current study inve stigated the possible involvement of PSD-95/SAP90 in determining MAC for is oflurane anesthesia. Methods: Sprague-Dawley rats mere pretreated intrathecally with PSD-95/SAP9 0 antisense oligodeoxyribonucleotide (ODN), sense ODN, missense ODN, or sal ine every 24 h for 4 days. After initial baseline determination of the MAC, NMDA or saline was injected intrathecally. Ten minutes later, MAC measurem ent was repeated. The rats also were evaluated for the presence of locomoto r dysfunction by intrathecal administration of NMDA or saline in the saline - and ODN-treated rats. Results: In the groups treated with antisense ODNs, but not in those treate d with sense or missense ODNs, there was a significant decrease in isoflura ne MAC that was not accompanied by marked changes in either blood pressure or heart rate, In the saline-treated group, intrathecal NMDA caused an incr ease in isoflurane MAC. In contrast, in the antisense ODN-treated group, in trathecal NMDA did not produce a significant change in isoflurane MAC. An N MDA-induced increase in blood pressure but not heart rate was found in both saline- and antisense ODN-treated groups. Locomotor activity was not chang ed in any of the treated animals. Conclusion: The results indicate not only a significant decrease in MAC for isoflurane but also an attenuation in the NMDA-induced increase in isoflur ane MAC in the PSD-95/SAP90 antisense-treated animals, which suggests that PSD-95/SAP90 may mediate the role of the NMDA receptor in determining the M AC of inhalational anesthetics.