MAC reduction after intrathecal coadministration of GABA_A agonist and glutamate antagonist in rats

Abstract

Purpose. It has been reported that intrathecal coadministration of a GABA_A agonist and a glutamate antagonist induces synergistic antinociceptive effects in rats. We hypothesized that this synergistic antinociceptive effect might induce a synergistic reduction in the minimum alveolar anesthetic concentration (MAC).

Methods. The MAC for sevoflurane was determined before and after intrathecal administration of muscimol (GABA_A agonist, 0.1–10 μg), AP-5 (N-methyl-d-aspartate [NMDA] antagonist, 0.1–10 μg), and YM872 (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid [AMPA] antagonist, 0.1–10 μg) in rats. The effects of coadministration of muscimol and AP-5 or YM872 on MAC reduction were also tested.

Results. Intrathecal administration of muscimol at doses of 1 and 10 μg significantly reduced the MAC by 34.5% ± 3.3% and 46.9% ± 4.4%, respectively (P < 0.01). Intrathecal administration of AP-5 at a dose of 10 μg and YM872 at a dose of 10 μg significantly reduced the MAC by 25.8% ± 2.4% and 31.4% ± 6.3%, respectively (P < 0.01). No additional reductions in MAC values were observed when a GABA_A agonist was combined with either an NMDA or an AMPA antagonist.

Conclusion. Intrathecal coadministration of a GABA_A agonist and an NMDA or AMPA antagonist, which has been reported to produce a synergistic antinociceptive effect, did not induce a synergistic reduction in the MAC. The antinociceptive effect may not be the predominant factor in the reduction of the MAC induced by these drugs.