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.