Central Cholinergic Depression Reduces MAC for Isoflurane in Rats

Zucker, Jonathan R.

doi:10.1213/00000539-199106000-00013

Cited by 31 publications

(9 citation statements)

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“…Moreover, peripheral administration of nicotine is known to activate nociceptors (54,55) and several lines of evidence have shown that muscarinic agonists enhance antinociceptive effects, which are blocked by pretreatment with M 1 , M 2 , or M 3 muscarinic receptorantagonists (56). In contrast, inhibition of the muscarinic signaling pathway induced by reducing ACh levels, inhibiting ACh release, or administering scopolamine in rat brains decreases the minimum alveolar anesthetic concentration of inhaled anesthetics (57). Several anesthetics, such as isoflurane, depress M 1 -and M 3 -receptor function (13,58).…”

Section: Effect Of Tramadol On Voltage-dependent Ion Channelsmentioning

confidence: 99%

Pharmacological Aspects of the Effects of Tramadol on G-Protein Coupled Receptors

2007

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Abstract. Tramadol is an analgesic that is used worldwide, but its mechanisms of action have not been elucidated. It has been speculated that tramadol acts primarily through the activation of µ-opioid receptors and the inhibition of monoamine reuptake. The majority of studies to date have focused on ion channels in the central nervous system as targets of anesthetics and analgesics. During the past decade, major advances have been made in our understanding of the physiology and pharmacology of G-protein coupled receptor (GPCR) signaling. Several studies have shown that GPCRs and ion channels are targets for analgesics and anesthetics. In particular, tramadol has been shown to affect GPCRs, including muscarinic acetylcholine receptors and 5-hydroxytryptamine receptors. Here, the effects of tramadol on monoamine transporters, GPCRs, and ion channels are presented, and recent research on the pharmacology of tramadol is discussed.

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Section: Effect Of Tramadol On Voltage-dependent Ion Channelsmentioning

confidence: 99%

Pharmacological Aspects of the Effects of Tramadol on G-Protein Coupled Receptors

2007

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“…Moreover, three cross-sectional population-based studies have demonstrated that anticholinergic drug intake is an important factor in determining the severity of cognitive impairment [15], [16], [17]. Because previous studies have shown that volatile anesthetics have anticholinergic properties [18], we hypothesized that pretreatment with the acetylcholinesterase inhibitor donepezil, which has been approved by the Food and Drug Administration (FDA) for the treatment of Alzheimer's disease, may prevent isoflurane-induced spatial memory impairment in aged mice.…”

Section: Introductionmentioning

confidence: 99%

Isoflurane-Induced Spatial Memory Impairment in Mice is Prevented by the Acetylcholinesterase Inhibitor Donepezil

Zhao

Wang

et al. 2011

PLoS ONE

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Although many studies have shown that isoflurane exposure impairs spatial memory in aged animals, there are no clinical treatments available to prevent this memory deficit. The anticholinergic properties of volatile anesthetics are a biologically plausible cause of cognitive dysfunction in elderly subjects. We hypothesized that pretreatment with the acetylcholinesterase inhibitor donepezil, which has been approved by the Food and Drug Administration (FDA) for the treatment of Alzheimer's disease, prevents isoflurane-induced spatial memory impairment in aged mice. In present study, eighteen-month-old mice were administered donepezil (5 mg/kg) or an equal volume of saline by oral gavage with a feeding needle for four weeks. Then the mice were exposed to isoflurane (1.2%) for six hours. Two weeks later, mice were subjected to the Morris water maze to examine the impairment of spatial memory after exposure to isoflurane. After the behavioral test, the mice were sacrificed, and the protein expression level of acetylcholinesterase (AChE), choline acetylase (ChAT) and α7 nicotinic receptor (α7-nAChR) were measured in the brain. Each group consisted of 12 mice. We found that isoflurane exposure for six hours impaired the spatial memory of the mice. Compared with the control group, isoflurane exposure dramatically decreased the protein level of ChAT, but not AChE or α7-nAChR. Donepezil prevented isoflurane-induced spatial memory impairments and increased ChAT levels, which were downregulated by isoflurane. In conclusions, pretreatment with the AChE inhibitor donepezil prevented isoflurane-induced spatial memory impairment in aged mice. The mechanism was associated with the upregulation of ChAT, which was decreased by isoflurane.

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“…Previous studies demonstrated that the release, presence, and activity of acetylcholine within the cerebral cortex, pontine reticular formation, and striatum are suppressed during general anesthesia 45–48 . Decreased cholinergic transmission lowers the minimum alveolar concentration for isoflurane in the rat 49 , while enhanced cholinergic tone in the brain can reverse isoflurane anesthesia 10 . Systemic or cortical application of atropine prevents NBM-mediated electroencephalogram desynchronization 50,51 .…”

Section: Discussionmentioning

confidence: 99%

Norepinephrine Infusion into Nucleus Basalis Elicits Microarousal in Desflurane-anesthetized Rats

et al. 2011

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Background The nucleus Basalis of Meynert of the basal forebrain has been implicated in the regulation of the state of consciousness across normal sleep-wake cycles. Here we investigated its role in the modulation of general anesthesia. Methods Rats were chronically implanted with bilateral infusion cannulae in the nucleus Basalis of Meynert and epidural electrodes to record the electroencephalogram in frontal and visual cortices. Animals were anesthetized with desflurane at a concentration required for the loss of righting reflex (4.6 ± 0.5%). Norepinephrine (17.8 nmol), or artificial cerebrospinal fluid was infused at 0.2 µl/min (1 µl total). Behavioral response to infusion was measured by scoring the orofacial, limb and head movements, and postural changes. Results Behavioral responses were higher after norepinephrine (2.1 ± 1) than artificial cerebrospinal fluid (0.63 ± 0.8) infusion (p < 0.01, t-test). Responses were brief (1–2 minutes), repetitive and more frequent after norepinephrine infusion (p < 0.0001, chi-square test). Electroencephalogram δ power decreased after norepinephrine in frontal (70 ± 7%) but not in visual cortex (p < 0.05, t-test). Simultaneously, electroencephalogram cross-approximate entropy between frontal and visual cortices increased from 3.17 ± 0.56 to 3.85 ± 0.29 after norepinephrine infusion (p < 0.01, t-test). Behavioral activation was predictable by the decrease in frontal δ power (logistic regression, p < 0.05). Conclusions Norepinephrine infusion into the nucleus Basalis of Meynert can modulate anesthetic depth presumably by ascending activation of the cortex. The transient nature of the responses suggests a similarity with micro-arousals normally observed during natural sleep, and may imply a mechanism for transient awareness under light anesthesia.

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Central Cholinergic Depression Reduces MAC for Isoflurane in Rats

Cited by 31 publications

References 0 publications

Pharmacological Aspects of the Effects of Tramadol on G-Protein Coupled Receptors

Pharmacological Aspects of the Effects of Tramadol on G-Protein Coupled Receptors

Isoflurane-Induced Spatial Memory Impairment in Mice is Prevented by the Acetylcholinesterase Inhibitor Donepezil

Norepinephrine Infusion into Nucleus Basalis Elicits Microarousal in Desflurane-anesthetized Rats

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