ArticleAnesthesia and analgesia2016
Physostigmine and Methylphenidate Induce Distinct Arousal States During Isoflurane General Anesthesia in Rats.
Article in Anesthesia and analgesia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- Current and Developing Approaches for Facilitating Emergence from General Anesthesia.Anesthesiology · 2025Review
- Parafacial GABAergic neurone ablation induces behavioural resistance to volatile anaesthetic-induced hypnosis without reducing sleep.British journal of anaesthesia · 2025Article
- Restoring consciousness with pharmacologic therapy: Mechanisms, targets, and future directions.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Continuous blood exchange in rats as a novel approach for experimental investigation.Scientific reports · 2024Article
- Time to Wake Up! The Ongoing Search for General Anesthetic Reversal Agents.Anesthesiology · 2024Article
- Selective optogenetic modulation of the PBN terminals in the lateral hypothalamic area and basal forebrain regulates emergence from isoflurane anesthesia in mice.BMC anesthesiology · 2023Article
- Modeling cortical synaptic effects of anesthesia and their cholinergic reversal.PLoS computational biology · 2022Article
- Historical and Modern Evidence for the Role of Reward Circuitry in Emergence.Anesthesiology · 2022Review
- Excitation of Putative Glutamatergic Neurons in the Rat Parabrachial Nucleus Region Reduces Delta Power during Dexmedetomidine but not Ketamine Anesthesia.Anesthesiology · 2021Article
- Differential effects of the novel neurosteroid hypnotic (3β,5β,17β)-3-hydroxyandrostane-17-carbonitrile on electroencephalogram activity in male and female rats.British journal of anaesthesia · 2021Article
- Cholinergic Modulation of General Anesthesia.Current neuropharmacology · 2021Article
- Cholinergic-Induced Specific Oscillations in the Medial Prefrontal Cortex to Reverse Propofol Anesthesia.Frontiers in neuroscience · 2021Article
- Robust alternative to the righting reflex to assess arousal in rodents.Scientific reports · 2020Article
- Neurotransmitter networks in mouse prefrontal cortex are reconfigured by isoflurane anesthesia.Journal of neurophysiology · 2020Article
- Novel neuroactive steroid with hypnotic and T-type calcium channel blocking properties exerts effective analgesia in a rodent model of post-surgical pain.British journal of pharmacology · 2020Article
- Delayed Emergence from Anesthesia: What We Know and How We Act.Local and regional anesthesia · 2020Review
- Article
- Basal Forebrain Cholinergic Activity Modulates Isoflurane and Propofol Anesthesia.Frontiers in neuroscience · 2020Article
- Towards a Comprehensive Understanding of Anesthetic Mechanisms of Action: A Decade of Discovery.Trends in pharmacological sciences · 2019Review
- Escape From Oblivion: Neural Mechanisms of Emergence From General Anesthesia.Anesthesia and analgesia · 2019Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAlthough emergence from general anesthesia is clinically treated as a passive process driven by the pharmacokinetics of drug clearance, agents that hasten recovery from general anesthesia may be useful for treating delayed emergence, emergence delirium, and postoperative cognitive dysfunction. Activation of central monoaminergic neurotransmission with methylphenidate has been shown to induce reanimation (active emergence) from general anesthesia. Cholinergic neurons in the brainstem and basal forebrain are also known to promote arousal. The objective of this study was to test the hypothesis that physostigmine, a centrally acting cholinesterase inhibitor, induces reanimation from isoflurane anesthesia in adult rats.
methodsThe dose-dependent effects of physostigmine on time to emergence from a standardized isoflurane general anesthetic were tested. It was then determined whether physostigmine restores righting during continuous isoflurane anesthesia. In a separate group of rats with implanted extradural electrodes, physostigmine was administered during continuous inhalation of 1.0% isoflurane, and the electroencephalogram changes were recorded. Finally, 2.0% isoflurane was used to induce burst suppression, and the effects of physostigmine and methylphenidate on burst suppression probability (BSP) were tested.
resultsPhysostigmine delayed time to emergence from isoflurane anesthesia at doses ≥0.2 mg/kg (n = 9). During continuous isoflurane anesthesia (0.9% ± 0.1%), physostigmine did not restore righting (n = 9). Blocking the peripheral side effects of physostigmine with the coadministration of glycopyrrolate (a muscarinic antagonist that does not cross the blood-brain barrier) produced similar results (n = 9 each). However, during inhalation of 1.0% isoflurane, physostigmine shifted peak electroencephalogram power from δ (<4 Hz) to θ (4-8 Hz) in 6 of 6 rats. During continuous 2.0% isoflurane anesthesia, physostigmine induced large, statistically significant decreases in BSP in 6 of 6 rats, whereas methylphenidate did not.
conclusionsUnlike methylphenidate, physostigmine does not accelerate time to emergence from isoflurane anesthesia and does not restore righting during continuous isoflurane anesthesia. However, physostigmine consistently decreases BSP during deep isoflurane anesthesia, whereas methylphenidate does not. These findings suggest that activation of cholinergic neurotransmission during isoflurane anesthesia produces arousal states that are distinct from those induced by monoaminergic activation.
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