The effect of halothane on thermosensitive neurons in the preoptic region of the anterior hypothalamus in acutely instrumented cats

Abstract

Normal thermoregulatory processes are significantly impaired by halothane anesthesia. However, the direct effects of halothane on thermosensitive neurons in the preoptic region of the anterior hypothalamus, a major thermoregulatory site, have not been previously investigated. Thirty-eight cats were anesthetized with α-chloralose (60 mg/kg) and urethane (600 mg/kg) and placed in stereotactic restraint. Stainless steel thermodes for highly selective local heating and cooling were stereotactically placed into the preoptic region with thermocouples used to monitor regional temperature. Using tungsten microelectrodes, 148 single neurons in the preoptic region were identified and subjected to local heating (to 42° C) and cooling (to 30°C). Eighteen percent (n = 27) in 15 different cats were classified as thermosensitive by accepted criteria (change in firing rate per degree centigrade of > 0.8 spikes · s-1 · ° C-1 or < -0.6 spikes · s-1 · ° C-1). Thermosensitive units were then subjected to graded concentrations of halothane (0.25-1.0% end-tidal), and local heating and cooling were repeated. The spontaneous firing rate (spikes per second) at 37° C of 21 warm-sensitive neurons was significantly (P < 0.05) reduced, to 65.5 ± 8.3, 42.6 ± 10.7, 28.0 ± 9.5, and 18.1 ± 6.0% of control at 0.25, 0.50, 0.75, and 1% halothane, respectively. Spontaneous firing rate returned to 99.5 ± 19.8% of control within 30 min after discontinuation of halothane. Thermosensitivity (change, per degree centigrade, in spikes per second) was also significantly reduced, to 33.3 ± 5.6, 28.5 ± 14.6, and 13.9 ± 6.6% of control at 0.50, 0.75 and 1.0% halothane (all P < 0.05 compared to control). Thermosensitivity returned to 97.0 ± 11% of control within 30 min after halothane. In order to assess the variability of neuron firing rates, the train of impulses produced by single neurons was subjected to statistical analysis of the time intervals between successive spikes (interspike interval analysis) to derive the autocorrelation function. The coefficient of variation (standard deviation / mean of interspike intervals), a normalized index of variability of firing rate data from single neurons, was unchanged by halothane administration. Processed electroencephalographic parameters (spectral edge 50, 80, 95, total activity, and percent activity in δ, θ, α, and β bands) did not show consistent changes with hypothalamic heating and cooling before or after halothane administration. The alterations in thermosensitive unit activity and impairment of hypothalamic thermal detection abilities produced by halothane may contribute to the altered thermoregulatory function observed during general anesthesia.