Activation of Brain Noradrenergic Neurons during Recovery from Halothane Anesthesia: Persistence of Phasic Activation after Clonidine

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α2-Adrenoceptor agonists, known as antihypertensive agents, may be used during general anesthesia for their anesthetic sparing action and to reduce the occurrence of side effects. Previous studies have shown that the brain's noradrenergic nucleus, locus coeruleus, is an important target in mediating the hypnotic action of α2 agonists. The authors studied the effects of recovery from halothane anesthesia on the electrical activity of locus coeruleus neurons to examine cellular substrates underlying the clinical effectivenes of α2 agonists.


Experiments were performed in locally anesthetized rats, whose circulatory and acid-base stabilities were ensured by mechanical ventilation and volume infusion. Locus coeruleus neurons were recorded continuously while the rats were anesthetized with halothane (1%) and/or after the halothane was discontinued.


Under the influence of halothane, locus coeruleus cells exhibited a slow, regular spontaneous discharge (1.95 ± 0.23 Hz), and contralateral foot or tail pinch elicited a prominent, phasic activation was blocked by local ejection of kynurenic acid, an excitatory amino acid antagonist, close to recorded neurons, but not by clonidine (up to 64 μg·kg-1). Thirty minutes after the halothane was discontinued, the mean firing rate of locus coeruleus neurons was increased by 87 ± 20%. This excitation resulted from a prominent increase in bursting activity (21 ± 5% of spikes in bursts vs. 4 ± 1%) and was reversed by halothane readministration. This activation also was reduced by local ejection of kynurenic acid. Halothane discontinuance revealed the reactivity of locus coeruleus neurons to nonnoxious, sensory stimuli, and considerably reduced the apparent potency of intravenous administration of clonidine to inhibit locus coeruleus activity (effective dose for 50% of maximal effect (ED2), 25.48 ± 8.26 μg·kg-1vs. 4.81 ± 0.80 μg·kg-1 under halothane). This decrease was caused by the persistence of bursting activity after the administration of clonidine, which was completely suppressed by readministration of halothane or local coeruleus neuronal activity via excitatory amino acid input, and this withdrawal-induced activity is characterized by a prominent burst (phasic) discharge; (2) that sedative doses of clonidine inhibit the tonic component of locus coeruleus activity but not the phasic activation of locus coeruleus neurons; and (3) that readministration of halothane or local ejection of an excitatory amino acid an tagonist fully suppresses the bursting activity unaffected by clonidine.

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