Effects of cholinomimetic injection into the brain stem reticular formation on halothane anesthesia and antinociception in rats.
The brain stem reticular formation plays an important role in determining consciousness and arousal. Modulation of cholinergic neurotransmission in this region alters the sleep-wake cycle. In the present study, we examined the effect of the direct application of cholinergic agents into the pontine reticular nucleus on anesthetic requirements and recovery and antinociception in rats. Sprague-Dawley rats were implanted with 24-gauge guide cannulas 1.0 mm above the oral portion of pontine reticular nucleus (PnO) while under pentobarbital anesthesia with the use of a stereotaxic apparatus. After recovery from surgery, animals were randomly assigned to one of the following protocols: minimum alveolar concentration (MAC), recovery time, tail-flick latency, or motor blockade. All measurements were performed after carbachol microinjection into the PnO after pretreatment with atropine or mecamylamine. Carbachol injection into the PnO significantly reduced MAC of halothane and prolonged recovery in a dose-dependent manner. Pretreatment with atropine reversed MAC reduction by carbachol, and both atropine and mecamylamine shortened recovery time under carbachol. In unanesthetized rats, carbachol produced antinociceptive effects as reflected by a change in tail-flick latency response. Atropine and mecamylamine inhibited antinociceptive effects of carbachol. These results suggest that cholinomimetic injection into the PnO modulates the anesthetic state produced by halothane, suggesting participation of this area in the mechanisms in the brain that generate the anesthetic state.
Ishizawa
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Department of Anesthesiology and Critical Care Medicine, Gifu University School of Medicine, Japan. ishizawa@mail.med.upenn.edu
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Dohi
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Shimonaka
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D000698:Analgesia; D000758:Anesthesia; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006221:Halothane / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology; D012154:Reticular Formation / Q000187:drug effects* / Q000502:physiology
D018685:Anesthetics, Inhalation; D011976:Receptors, Muscarinic; D001285:Atropine; D002217:Carbachol; D006221:Halothane