ACTIVATION OF BRAIN NORADRENERGIC NEURONS DURING RECOVERY FROM HALOTHANE ANESTHESIA

Background. Alpha2-Adrenoceptor agonists, known as antihypertensive ag ents, may be used during general anesthesia for their anesthetic spari ng action and to reduce the occurrence of side effects. Previous studi es have shown that the brain's noradrenergic nucleus, locus coeruleus, is an important target in mediating the hypnotic action of alpha2 ago nists. The authors studied the effects of recovery from halothane anes thesia on the electrical activity of locus coeruleus neurons to examin e cellular substrates underlying the clinical effectiveness of alpha2 agonists. Methods: Experiments were performed in locally anesthetized rats, whose circulatory and acid-base stabilities were ensured by mech anical ventilation and volume infusion. Locus cocruleus neurons were r ecorded continuously while the rats were anesthetized with halothane ( 1%) and/or after the halothane was discontinued. Results: Under the in fluence of halothane, locus coeruleus cells exhibited a slow, regular spontaneous discharge (1.95 +/- 0.23 Hz), and contralateral foot or ta il pinch elicited a prominent, phasic activation in locus cocruleus ne urons. Such phasic activation was blocked by local ejection of kynuren ic acid, an excitatory amino acid antagonist, close to recorded neuron s, but not by clonidine (up to 64 mug . kg-1). Thirty minutes after th e halothane was discontinued, the mean firing rate of locus coeruleus neurons was increased by 87 +/- 20%. This excitation resulted from a p rominent increase in bursting activity (21 +/- 5% of spikes in bursts vs. 4 +/- 1%) and was reversed by halothane readministration. This act ivation also was reduced by local ejection of kynurenic acid. Halothan e discontinuance revealed the reactivity of locus coeruleus neurons to nonnoxious, sensory stimuli, and considerably reduced the apparent po tency of intravenous administration of clonidine to inhibit locus coer uleus activity (effective dose for 50% of maximal effect (ED50), 2 5.4 8 +/- 8.26 mug . kg-1 vs. 4.81 +/- 0.80 mug . kg-1 under halothane). T his decrease was caused by the persistence of bursting activity after the administration of clonidine, which was completely suppressed by re administration of halothane or local application of kynurenic acid. Co nclusion: The data demonstrate: (1) that halothane withdrawal increase s locus coeruleus neuronal activity via excitatory amino acid input, a nd this withdrawal-induced activity is characterized by a prominent bu rst (phasic) discharge; (2) that sedative doses of clonidine inhibit t he tonic component of locus coeruleus activity but not the phasic acti vation of locus coeruleus neurons; and (3) that readministration of ha lothane or local ejection of an excitatory amino acid antagonist fully suppresses the bursting activity unaffected by clonidine.