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


METHODS
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.


METHODS
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METHODS
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METHODS
N/A.


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.
Lydic
Ralph
R
Department of Anesthesiology, University of Michigan, Ann Arbor 48109, USA. rlydic@umich.edu
Baghdoyan
Helen A
HA
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002415:Cats; D002851:Chromatography, High Pressure Liquid; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004569:Electroencephalography; D004576:Electromyography; D004585:Electrooculography; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D017286:Polysomnography; D011149:Pons / Q000187:drug effects* / Q000378:metabolism*; D012119:Respiration / Q000187:drug effects*; D012154:Reticular Formation / Q000187:drug effects* / Q000378:metabolism*; D012893:Sleep Wake Disorders / Q000139:chemically induced*; D012895:Sleep, REM / Q000187:drug effects; D013997:Time Factors; D014851:Wakefulness / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D016202:N-Methylaspartate; D007649:Ketamine; D016291:Dizocilpine Maleate; D000109:Acetylcholine