GLYCINE RECEPTORS ARE INVOLVED IN ANESTHETIC EFFECTS OF HALOTHANE ON SPINAL DORSAL HORN LOW-THRESHOLD NEURONS IN THE RAT

Abstract

S471 INTRODUCTION: We have been studying a series of effects of anesthetics on spinal dorsal horn neurons. These suggest that reduction in low-threshold receptive field (RF) size, which is induced by inhalation anesthetics, is in part mediated by GABAA receptors, and that other transmitter systems are possibly responsible for the additional effect. In the CNS the major inhibitory neurotransmitters are thought to be GABA and glycine: GABA is predominant in the brain and glycine predominates in the spinal cord [1]. Thus, glycine receptors may be involved in anesthetic action of halothane within the spinal cord. The present study was designed to examine the effects of the glycine receptor antagonist strychnine on halothane-induced reduction of low-threshold RF size. METHODS: This protocol was approved by our institutional Animal Care and Use Committee. Extracellular activity of single spinal dorsal horn neurons was recorded in spinal cord-transected and decerebrated Sprague-Dawley rats (320-450g). Arterial blood pressure and end-tidal CO2 were monitored throughout the experiment. The low-threshold RF size was mapped in the unanesthetized state and in the presence of 1.1% (1 MAC) halothane. Animals then received i.v. strychnine to a cumulative dose of 2.0 mg/kg. Statistical significance was assessed by ANOVA and Bonferroni test with P value < 0.05 considered significant. RESULTS: In the absence of halothane, cumulative doses up to 2.0 mg/kg of strychnine did not affect RF size (107 +/- 10% of control, n=7), but it produced a significant partial, but not complete, reversal of halothane-induced reduction of the low-threshold RF size in a dose-related manner (Figure 1, n=8).Figure 1CONCLUSIONS: These results suggest that halothane reduction of low-threshold RF size is due in part to interactions at glycine receptors. As we have shown with GABAA and serotonin, each of these inhibitors only partially alters the neuronal responses, suggesting a complex pharmacology rather than a unitary mechanism of action. Supported, in part, by NIH GM 44954.