Blockade of 5-HT2A and/or 5-HT2C receptors modulates sevoflurane-induced immobility

Blockade of 5-hydroxytryptamine (5-HT)(2A) receptors reportedly mediates or modulates the ability of isoflurane to produce immobility during noxious stimulation and would thereby influence MAC (the minimum alveolar concentration required to suppress movement in response to noxious stimulation in 50% of subjects). However, no data are yet available regarding the role of this receptor in the immobilizing action of sevoflurane. In this study, we examined how prior intraperitoneal administration of either the 5-HT2A receptor antagonist altanserin or the 5-HT2C/2B receptor antagonist SB 206553 might affect sevoflurane MAC in rats. Three groups of six male Wistar rats weighing 250-350 g each received one of the following drugs dissolved in dimethyl sulfoxide intraperitoneally 30 min before MAC testing: (1) altanserin 10 mg/kg; (2) SB 206553 10 mg/kg; (3) no drug (vehicle control). MAC was defined as the average of the concentrations that just prevented or just permitted movement in response to clamping the tail for 1 min. The rank order of MAC values obtained after intraperitoneal drug pretreatment and sevoflurane exposure was altanserin < SB 206553 < vehicle control. Considering the low levels of 5-HT2B receptors within the CNS, this result suggests that 5-HT2A and the 5-HT2C receptors are present within the neural circuitry influencing sevoflurane MAC. Blockade of 5-HT2A and/or 5-HT2C receptors may modulate the immobility produced by sevoflurane during noxious stimulation.