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Dextroamphetamine (but Not Atomoxetine) Induces Reanimation from General Anesthesia: Implications for the Roles of Dopamine and Norepinephrine in Active Emergence.

Kenny JD, Taylor NE, Brown EN, Solt K - PLoS ONE (2015)

Bottom Line: The difference was statistically significant.Although atomoxetine reduced mean emergence time to 566 sec (n = 8), this decrease was not statistically significant.We hypothesize that dextroamphetamine is more likely than atomoxetine to be clinically useful for restoring consciousness in anesthetized patients, mainly due to its stimulation of dopaminergic neurotransmission.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.

ABSTRACT
Methylphenidate induces reanimation (active emergence) from general anesthesia in rodents, and recent evidence suggests that dopaminergic neurotransmission is important in producing this effect. Dextroamphetamine causes the direct release of dopamine and norepinephrine, whereas atomoxetine is a selective reuptake inhibitor for norepinephrine. Like methylphenidate, both drugs are prescribed to treat Attention Deficit Hyperactivity Disorder. In this study, we tested the efficacy of dextroamphetamine and atomoxetine for inducing reanimation from general anesthesia in rats. Emergence from general anesthesia was defined by return of righting. During continuous sevoflurane anesthesia, dextroamphetamine dose-dependently induced behavioral arousal and restored righting, but atomoxetine did not (n = 6 each). When the D1 dopamine receptor antagonist SCH-23390 was administered prior to dextroamphetamine under the same conditions, righting was not restored (n = 6). After a single dose of propofol (8 mg/kg i.v.), the mean emergence times for rats that received normal saline (vehicle) and dextroamphetamine (1 mg/kg i.v.) were 641 sec and 404 sec, respectively (n = 8 each). The difference was statistically significant. Although atomoxetine reduced mean emergence time to 566 sec (n = 8), this decrease was not statistically significant. Spectral analysis of electroencephalogram recordings revealed that dextroamphetamine and atomoxetine both induced a shift in peak power from δ (0.1-4 Hz) to θ (4-8 Hz) during continuous sevoflurane general anesthesia, which was not observed when animals were pre-treated with SCH-23390. In summary, dextroamphetamine induces reanimation from general anesthesia in rodents, but atomoxetine does not induce an arousal response under the same experimental conditions. This supports the hypothesis that dopaminergic stimulation during general anesthesia produces a robust behavioral arousal response. In contrast, selective noradrenergic stimulation causes significant neurophysiological changes, but does not promote behavioral arousal during general anesthesia. We hypothesize that dextroamphetamine is more likely than atomoxetine to be clinically useful for restoring consciousness in anesthetized patients, mainly due to its stimulation of dopaminergic neurotransmission.

No MeSH data available.


Related in: MedlinePlus

Atomoxetine administration induces significant EEG changes during continuous sevoflurane anesthesia.(A) Representative 60-second time-domain EEG recording from an individual rat during continuous sevoflurane anesthesia, with time zero indicating the administration of atomoxetine (3 mg/kg IV). The EEG pattern rapidly changes to a low amplitude, high frequency rhythm after the administration of atomoxetine. (B) Representative time-frequency domain spectrogram computed from 15 minutes of EEG data. A prompt shift in peak power from δ to θ is observed after the administration of atomoxetine. (C) Group power spectral density from all rats (n = 3), with shaded areas indicating 95% confidence intervals. Before atomoxetine administration (blue), δ power was dominant during continuous sevoflurane anesthesia. After atomoxetine administration (red), statistically significant reductions in power occurred at most frequencies below 10 Hz, and peak power was shifted to θ.
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pone.0131914.g005: Atomoxetine administration induces significant EEG changes during continuous sevoflurane anesthesia.(A) Representative 60-second time-domain EEG recording from an individual rat during continuous sevoflurane anesthesia, with time zero indicating the administration of atomoxetine (3 mg/kg IV). The EEG pattern rapidly changes to a low amplitude, high frequency rhythm after the administration of atomoxetine. (B) Representative time-frequency domain spectrogram computed from 15 minutes of EEG data. A prompt shift in peak power from δ to θ is observed after the administration of atomoxetine. (C) Group power spectral density from all rats (n = 3), with shaded areas indicating 95% confidence intervals. Before atomoxetine administration (blue), δ power was dominant during continuous sevoflurane anesthesia. After atomoxetine administration (red), statistically significant reductions in power occurred at most frequencies below 10 Hz, and peak power was shifted to θ.

Mentions: A representative time-series EEG recording from an individual rat during continuous sevoflurane anesthesia is shown in Fig 5A. Similar to dextroamphetamine, the administration of atomoxetine (3 mg/kg IV) rapidly decreased the amplitude and increased the frequency of the EEG waveform. A spectrogram computed from the EEG data (Fig 5B) shows that the administration of atomoxetine (3 mg/kg IV) induced an abrupt shift in peak power from δ to θ frequencies. The group power spectral density from all three rats (Fig 5C) shows that atomoxetine induced a statistically significant decrease in power at most frequencies below 10 Hz, and shifted peak power from δ to θ.


Dextroamphetamine (but Not Atomoxetine) Induces Reanimation from General Anesthesia: Implications for the Roles of Dopamine and Norepinephrine in Active Emergence.

Kenny JD, Taylor NE, Brown EN, Solt K - PLoS ONE (2015)

Atomoxetine administration induces significant EEG changes during continuous sevoflurane anesthesia.(A) Representative 60-second time-domain EEG recording from an individual rat during continuous sevoflurane anesthesia, with time zero indicating the administration of atomoxetine (3 mg/kg IV). The EEG pattern rapidly changes to a low amplitude, high frequency rhythm after the administration of atomoxetine. (B) Representative time-frequency domain spectrogram computed from 15 minutes of EEG data. A prompt shift in peak power from δ to θ is observed after the administration of atomoxetine. (C) Group power spectral density from all rats (n = 3), with shaded areas indicating 95% confidence intervals. Before atomoxetine administration (blue), δ power was dominant during continuous sevoflurane anesthesia. After atomoxetine administration (red), statistically significant reductions in power occurred at most frequencies below 10 Hz, and peak power was shifted to θ.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4492624&req=5

pone.0131914.g005: Atomoxetine administration induces significant EEG changes during continuous sevoflurane anesthesia.(A) Representative 60-second time-domain EEG recording from an individual rat during continuous sevoflurane anesthesia, with time zero indicating the administration of atomoxetine (3 mg/kg IV). The EEG pattern rapidly changes to a low amplitude, high frequency rhythm after the administration of atomoxetine. (B) Representative time-frequency domain spectrogram computed from 15 minutes of EEG data. A prompt shift in peak power from δ to θ is observed after the administration of atomoxetine. (C) Group power spectral density from all rats (n = 3), with shaded areas indicating 95% confidence intervals. Before atomoxetine administration (blue), δ power was dominant during continuous sevoflurane anesthesia. After atomoxetine administration (red), statistically significant reductions in power occurred at most frequencies below 10 Hz, and peak power was shifted to θ.
Mentions: A representative time-series EEG recording from an individual rat during continuous sevoflurane anesthesia is shown in Fig 5A. Similar to dextroamphetamine, the administration of atomoxetine (3 mg/kg IV) rapidly decreased the amplitude and increased the frequency of the EEG waveform. A spectrogram computed from the EEG data (Fig 5B) shows that the administration of atomoxetine (3 mg/kg IV) induced an abrupt shift in peak power from δ to θ frequencies. The group power spectral density from all three rats (Fig 5C) shows that atomoxetine induced a statistically significant decrease in power at most frequencies below 10 Hz, and shifted peak power from δ to θ.

Bottom Line: The difference was statistically significant.Although atomoxetine reduced mean emergence time to 566 sec (n = 8), this decrease was not statistically significant.We hypothesize that dextroamphetamine is more likely than atomoxetine to be clinically useful for restoring consciousness in anesthetized patients, mainly due to its stimulation of dopaminergic neurotransmission.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts, United States of America.

ABSTRACT
Methylphenidate induces reanimation (active emergence) from general anesthesia in rodents, and recent evidence suggests that dopaminergic neurotransmission is important in producing this effect. Dextroamphetamine causes the direct release of dopamine and norepinephrine, whereas atomoxetine is a selective reuptake inhibitor for norepinephrine. Like methylphenidate, both drugs are prescribed to treat Attention Deficit Hyperactivity Disorder. In this study, we tested the efficacy of dextroamphetamine and atomoxetine for inducing reanimation from general anesthesia in rats. Emergence from general anesthesia was defined by return of righting. During continuous sevoflurane anesthesia, dextroamphetamine dose-dependently induced behavioral arousal and restored righting, but atomoxetine did not (n = 6 each). When the D1 dopamine receptor antagonist SCH-23390 was administered prior to dextroamphetamine under the same conditions, righting was not restored (n = 6). After a single dose of propofol (8 mg/kg i.v.), the mean emergence times for rats that received normal saline (vehicle) and dextroamphetamine (1 mg/kg i.v.) were 641 sec and 404 sec, respectively (n = 8 each). The difference was statistically significant. Although atomoxetine reduced mean emergence time to 566 sec (n = 8), this decrease was not statistically significant. Spectral analysis of electroencephalogram recordings revealed that dextroamphetamine and atomoxetine both induced a shift in peak power from δ (0.1-4 Hz) to θ (4-8 Hz) during continuous sevoflurane general anesthesia, which was not observed when animals were pre-treated with SCH-23390. In summary, dextroamphetamine induces reanimation from general anesthesia in rodents, but atomoxetine does not induce an arousal response under the same experimental conditions. This supports the hypothesis that dopaminergic stimulation during general anesthesia produces a robust behavioral arousal response. In contrast, selective noradrenergic stimulation causes significant neurophysiological changes, but does not promote behavioral arousal during general anesthesia. We hypothesize that dextroamphetamine is more likely than atomoxetine to be clinically useful for restoring consciousness in anesthetized patients, mainly due to its stimulation of dopaminergic neurotransmission.

No MeSH data available.


Related in: MedlinePlus