Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 12224840

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

Ralph Lydic·Helen A Baghdoyan
View original source ↗Export metadata ↓

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.

Explore related subjects

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

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

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/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2004

Effects of alpha calcitonin gene-related peptide in human bronchial smooth muscle and pulmonary artery.

Although airway and pulmonary vessel tone are regulated predominantly by cholinergic and adrenergic impulses, biologically active peptides such as calcitonin gene-related peptide (CGRP) may significantly influence human smooth muscle tone in normal and pathophysiological states. In the present study, the expression of CGRP and its receptor CGRPR-1 and the biological effect of the peptide were investigated in human airways and pulmonary arteries. Immunohistochemistry revealed the presence of CGRP in human airway nerves and neuro-epithelial cells, whereas the receptor was found in epithelial cells and smooth muscle myocytes of the bronchi and in pulmonary artery endothelium. On precontracted bronchi (3-4 mm in diameter) alpha-CGRP (0.01-10 nM) caused a concentration-dependent contraction on epithelium-denuded bronchi, whereas no significant effect was recorded in bronchi with intact epithelium. In pulmonary arteries (2-6 mm in diameter), alpha-CGRP caused a concentration-dependent relaxation of endothelium intact and denuded vessels. Pre-treatment with indomethacin, but not with l-NAME, prevented the relaxation induced by alpha-CGRP in pulmonary arteries suggesting that prostaglandins but not nitric oxide (NO) are involved in the intracellular signal transduction pathway. The effects induced by alpha-CGRP in bronchi and vessels were prevented by application of the antagonist CGRP((8-37)). In summary, the present studies examined the biological function of CGRP in human airways and demonstrated a constrictory effect of CGRP only in epithelium-denuded airway smooth muscle indicating an alteration of CGRP airway effects in respiratory tract pathological states with damaged epithelium such as chronic obstructive pulmonary disease or bronchial asthma.

Acetylcholine↗
PubMed2004

Acetylcholine-induced calcium signalling in adrenaline- and noradrenaline-containing adrenal chromaffin cells.

Adrenal chromaffin cells secrete catecholamines in response to cholinergic receptor activation by acetylcholine (ACh). Characteristics of Ca(2+) transients induced by activation of nicotinic (nAChRs) and muscarinic (mAChRs) receptors were analyzed using Fura-2 fluorescent measurements on rat chromaffin cells. We first found two populations of chromaffin cells, which differently responded on AChR stimulation. In the first group (n-cells), consecutive ACh applications evoked persistent Ca(2+) transients, whereas desensitizing transients were observed in the other group (m-cells). The AChR agonists and antagonists precisely imitated or abolished the ACh action on n- and m-type cells, respectively. Cytochemical staining showed that n-cells contained adrenaline, whereas m-cells-noradrenaline. Thus, for the first time we found that nAChRs and mAChRs are differentially expressed in adrenergic and noradrenergic chromaffin cells, respectively. Our data suppose that chromaffin cells can be differentially regulated by incoming ACh signals and in such way release different substances-adrenaline and noradrenaline.

Acetylcholine↗
PubMed2004

Cardiovascular effects of methyleugenol, a natural constituent of many plant essential oils, in normotensive rats.

Cardiovascular effects of intravenous (i.v.) treatment with methyleugenol (ME), a natural constituent of many plant essential oils, were investigated in normotensive rats. Additionally this study examined (I) whether the autonomic nervous system is involved in the mediation of ME-induced changes in mean aortic pressure (MAP) and heart rate (HR), and (II) whether the hypotensive effects of ME could result from its vasodilatory effects directly upon vascular smooth muscle. In both pentobarbital-anesthetized and conscious rats, i.v. bolus injections of ME (1 to 10 mg/kg) elicited similar and dose-dependent decreases in MAP. In anesthetized rats, ME decreased HR only at the highest dose (10 mg/kg), while changes of this parameter were not uniform in conscious rats. Pretreatment of anesthetized rats with bilateral vagotomy significantly reduced the bradycardia response to ME (10 mg/kg) without affecting the hypotension. In conscious rats, i.v. pretreatment with methylatropine (1 mg/kg) or hexamethonium (30 mg/kg) had no significant effect on ME-induced hypotension. In rat isolated thoracic aorta preparations, ME (0.006-1.68 mM) induced a concentration-dependent reduction of potassium (60 mM)-induced contraction. This is the first physiological evidence that i.v. treatment with ME in either anesthetized or conscious rats elicits hypotension; an effect that seems related to an active vascular relaxation rather than withdrawal of sympathetic tone.

Acetylcholine↗