Partial antagonism of propofol anaesthesia by physostigmine in rats is associated with potentiation of fast (80–200 Hz) oscillations in the thalamus

Reed, Sean J.; Plourde, Gilles; Tobin, Stephanie; Chapman, C. Andrew

doi:10.1093/bja/aes432

Cited by 15 publications

(15 citation statements)

References 23 publications

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“…These findings suggest that the peripheral muscarinic side effects of physostigmine are not the reason for the lack of reanimation observed with physostigmine. The present results are consistent with the report by Reed et al 28 who found that the combination of physostigmine and glycopyrrolate (at the same doses used in this study) does not restore righting in rats during continuous propofol anesthesia. Because glycopyrrolate does not cross the blood-brain barrier, 14 the presence or absence of glycopyrrolate should not affect the electroencephalogram results.…”

Section: Discussionsupporting

confidence: 93%

“…This is because there is currently no standard arousal scoring system in the literature, although several groups have devised such systems in an effort to refine measures of the anesthetized state. 8,26-28 Furthermore, because physostigmine can produce significant effects at the neuromuscular junction, it is difficult to distinguish whether minor peripheral movements in the absence of righting represent physostigmine-induced muscle twitches, or a true change in arousal state. Although the highest dose of physostigmine (0.4 mg/kg) co-administered with glycopyrrolate (0.08 mg/kg) caused more muscle twitching than lower doses of physostigmine (0.1-0.2 mg/kg), these movements were distinct from the purposeful movements (e.g.…”

Section: Discussionmentioning

confidence: 99%

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Physostigmine and Methylphenidate Induce Distinct Arousal States During Isoflurane General Anesthesia in Rats

Kenny

Chemali

Cotten

et al. 2016

Anesthesia &Amp; Analgesia

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Background Although 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 post-operative 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. Methods The 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. Results Physostigmine 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 co-administration 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 6/6 rats. During continuous 2.0% isoflurane anesthesia, physostigmine induced large, statistically significant decreases in BSP in 6/6 rats, whereas methylphenidate did not. Conclusions Unlike 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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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Physostigmine and Methylphenidate Induce Distinct Arousal States During Isoflurane General Anesthesia in Rats

Kenny

Chemali

Cotten

et al. 2016

Anesthesia &Amp; Analgesia

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“…The subcortical broadband gamma reduction confirms similar findings in rodent studies (Reed et al, 2013), and in one small series of thalamic recordings in humans (Verdonck et al, 2014). Broadband gamma power in cortex is thought to be an index of local neural activity and a surrogate for neural spiking (Miller et al, 2007, Manning et al, 2009).…”

Section: Discussionsupporting

confidence: 87%

Motor System Interactions in the Beta Band Decrease during Loss of Consciousness

Swann

Hemptinne

Maher³

et al. 2016

Journal of Cognitive Neuroscience

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Communication between brain areas and how they are influenced by changes in consciousness are not fully understood. One hypothesis is that brain areas communicate via oscillatory processes, utilizing network-specific frequency bands, that can be measured with metrics that reflect between-region interactions, such as coherence and phase amplitude coupling (PAC). To evaluate this hypothesis, and understand how these interactions are modulated by state changes, we analyzed electrophysiological recordings in humans at different nodes of one well-studied brain network: the basal ganglia-thalamo-cortical (BGTC) loops of the motor system, during loss of consciousness induced by anesthesia. We recorded simultaneous electrocorticography (ECoG) over primary motor cortex (M1) with local field potentials (LFPs) from subcortical motor regions (either basal ganglia or thalamus) in 15 movement disorder patients during anesthesia (propofol) induction as a part of their surgery for deep brain stimulation. We observed reduced coherence and PAC between M1 and the subcortical nuclei, which was specific to the beta band (~18-24 Hz). The fact that this pattern occurs selectively in beta underscores the importance of this frequency band in the motor system, and supports the idea that oscillatory interactions at specific frequencies are related to the capacity for normal brain function and behavior.

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“…The arousal scoring system was adapted from Reed et al (54). Leg, head, and whisker movements were scored as absent, mild, or moderate in intensity (0, 1, or 2, respectively) during 30 min of optical VTA stimulation while mice continuously inhaled 0.8 to 0.9% isoflurane.…”

Section: Discussionmentioning

confidence: 99%

“…The person who conducted the scoring was blinded to the experimental intervention (e.g., ChR2+ vs. ChR2−; saline vs. SCH-23390) to prevent biasing. After optical stimulation was initiated, the animals were observed for signs of arousal and scored using an adaptation of the method of Reed et al (54). Spontaneous movements of the limbs, head, and whiskers were recorded on an itemized scoring sheet as absent, mild, or moderate in intensity (0, 1, or 2, respectively).…”

Section: Methodsmentioning

confidence: 99%

Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia

Taylor

Dort

Kenny

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

208

179

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Dopamine (DA) promotes wakefulness, and DA transporter inhibitors such as dextroamphetamine and methylphenidate are effective for increasing arousal and inducing reanimation, or active emergence from general anesthesia. DA neurons in the ventral tegmental area (VTA) are involved in reward processing, motivation, emotion, reinforcement, and cognition, but their role in regulating wakefulness is less clear. The current study was performed to test the hypothesis that selective optogenetic activation of VTA DA neurons is sufficient to induce arousal from an unconscious, anesthetized state. Floxed-inverse (FLEX)-Channelrhodopsin2 (ChR2) expression was targeted to VTA DA neurons in DA transporter (DAT)-cre mice (ChR2+ group; n = 6). Optical VTA stimulation in ChR2+ mice during continuous, steady-state general anesthesia (CSSGA) with isoflurane produced behavioral and EEG evidence of arousal and restored the righting reflex in 6/6 mice. Pretreatment with the D1 receptor antagonist SCH-23390 before optical VTA stimulation inhibited the arousal responses and restoration of righting in 6/6 ChR2+ mice. In control DAT-cre mice, the VTA was targeted with a viral vector lacking the ChR2 gene (ChR2− group; n = 5). VTA optical stimulation in ChR2− mice did not restore righting or produce EEG changes during isoflurane CSSGA in 5/5 mice. These results provide compelling evidence that selective stimulation of VTA DA neurons is sufficient to induce the transition from an anesthetized, unconscious state to an awake state, suggesting critical involvement in behavioral arousal.anesthesia | ventral tegmental area | dopamine | optogenetics | arousal

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Partial antagonism of propofol anaesthesia by physostigmine in rats is associated with potentiation of fast (80–200 Hz) oscillations in the thalamus

Cited by 15 publications

References 23 publications

Physostigmine and Methylphenidate Induce Distinct Arousal States During Isoflurane General Anesthesia in Rats

Physostigmine and Methylphenidate Induce Distinct Arousal States During Isoflurane General Anesthesia in Rats

Motor System Interactions in the Beta Band Decrease during Loss of Consciousness

Optogenetic activation of dopamine neurons in the ventral tegmental area induces reanimation from general anesthesia

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