Effects of Ablation of Serotonin or Norepinephrine Brain-stem Areas on Halothane and Cyclopropane MACs in Rats

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Abstract
General anesthesia might result from interruption of neural transmission in discrete areas of brain rather than from a generalized depression of transmission. Anesthetics selectively altered neurotransmitter concentrations or glucose metabolism in specific regions in the brain. Whether anesthetic requirement would be altered by destruction of selected nuclei was questioned. Bilateral destruction of a large norepinephrine cell-body area, the locus coeruleus in the rat, decreased halothane MAC [minimum anesthetic concentration] from 1.13-0.78% (P .ltoreq. 0.01) and cyclopropane MAC from 20.5-16.1% (P .ltoreq. 0.001) compared with sham-operated littermates of equal wt. Ablation of the locus coeruleus did not change hypothalamic norepinephrine content, but decreased cortical norepinephrine levels by 80%. Destruction of the ventral bundle, which supplies approximately 40% of the norepinephrine in the central gray catecholamine area, decreased halothane MAC 35% (P .ltoreq. 0.001) and cyclopropane MAC 15% (P .ltoreq. 0.01). Rats that had ventral-bundle lesions weighed 18% less (P .ltoreq. 0.001) than controls. Ventral-bundle lesions decreased hypothalamic norepinephrine by 85% without altering cortical norepinephrine. Lesions in the serotonin-rich nucleus raphe dorsalis decreased halothane MAC 25% (P .ltoreq. 0.02) and cyclopropane MAC 16% (P .ltoreq. 0.01). These lesions decreased hypothalamic serotonin content by 40%, and cortical serotonin content by 80%. Although destruction of individual nuclei significantly decreased anesthetic requirement, lesions in no one area altered MAC by more than 35%. That general anesthesia results from discrete rather than generalized depression of transmission is thus supported, but not proven.