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PubMed · 12224840

Ketamine and MK-801 decrease acetylcholine release in the pontine reticular formation, slow breathing, and disrupt sleep.

Ralph Lydic·Helen A Baghdoyan
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Abstract

STUDY OBJECTIVES: Ketamine induces a dissociated state of consciousness by binding to the phencyclidine binding site within the ion channel gated by the N-methyl-D-aspartate (NMDA) receptor. The brain regions and neurotransmitter systems mediating ketamine-induced alterations in arousal remain incompletely understood. This study used in vivo microdialysis to test the hypothesis that ketamine alters acetylcholine (ACh) release in the medial pontine reticular formation (mPRF). DESIGN: Acetylcholine (ACh) release, sleep, and breathing were quantified following systemic ketamine administration. Microdialysis was used to deliver the NMDA-channel blocker dizocilpine maleate (MK-801) and the R(-)-isomer of ketamine into the mPRF while measuring ACh release. SETTING: N/A. PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Systemically administered ketamine disrupted normal sleep-cycle organization, reduced mPRF ACh release, and significantly slowed rate of breathing. Dialysis delivery of MK-801 to the mPRF significantly decreased respiratory rate and mPRF ACh release. Dialysis delivery to the mPRF of the R(-)-ketamine isomer significantly decreased mPRF ACh release. CONCLUSIONS: Decreased mPRF ACh release caused by systemically administered ketamine was mimicked by mPRF dialysis delivery of MK-801 and the R(-)-ketamine isomer. These data are consistent with the conclusion that systemically administered ketamine may alter arousal and breathing, in part, by altering cholinergic neurotransmission in the mPRF.

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AcetylcholineAnimalsCatsChromatography, High Pressure LiquidDizocilpine MaleateElectroencephalographyElectromyographyElectrooculographyExcitatory Amino Acid AntagonistsKetamineMaleN-MethylaspartatePolysomnographyPonsRespirationReticular FormationSleep Wake DisordersSleep, REMTime FactorsWakefulnessJournal ArticleResearch Support, U.S. Gov't, P.H.S.

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Ralph Lydic, Helen A Baghdoyan. 2002-09-15. Ketamine and MK-801 decrease acetylcholine release in the pontine reticular formation, slow breathing, and disrupt sleep.. https://pubmed.ncbi.nlm.nih.gov/12224840/

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