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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

Dextroamphetamine significantly decreases time to emergence from propofol anesthesia, but atomoxetine does not.(A) Rats received a bolus of propofol (8 mg/kg IV), followed by normal saline (vehicle), atomoxetine (1 mg/kg IV) or dextroamphetamine (1 mg/kg IV). Time to emergence was defined as the time from administration of propofol to return of righting. (B) Scatter plot of time to emergence for rats that received normal saline, dextroamphetamine, and atomoxetine after propofol. The lines represent mean values. Dextroamphetamine caused a statistically significant decrease in time to emergence compared to normal saline, whereas atomoxetine did not.
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pone.0131914.g002: Dextroamphetamine significantly decreases time to emergence from propofol anesthesia, but atomoxetine does not.(A) Rats received a bolus of propofol (8 mg/kg IV), followed by normal saline (vehicle), atomoxetine (1 mg/kg IV) or dextroamphetamine (1 mg/kg IV). Time to emergence was defined as the time from administration of propofol to return of righting. (B) Scatter plot of time to emergence for rats that received normal saline, dextroamphetamine, and atomoxetine after propofol. The lines represent mean values. Dextroamphetamine caused a statistically significant decrease in time to emergence compared to normal saline, whereas atomoxetine did not.

Mentions: Fig 2A shows the protocol for this experiment. Forty-five seconds after a single dose of propofol (8 mg/kg IV), normal saline (vehicle), dextroamphetamine (1 mg/kg IV) or atomoxetine (1 mg/kg IV) was administered, and time to emergence was recorded. Fig 2B shows a scatter plot of time to emergence after propofol for the normal saline, dextroamphetamine, and atomoxetine groups. The mean time to emergence for the normal saline group was 641 sec (95% CI: 530 to 759 sec, n = 8). In the dextroamphetamine group, mean time to emergence was 404 sec (95% CI: 371 to 439 sec, n = 8), and this reduction was statistically significant (mean difference: 237 sec; 95% CI: 121 to 358 sec). In the atomoxetine group, mean time to emergence was 566 sec (95% CI: 468 to 678 sec, n = 8) but this decrease in comparison to the normal saline group was not statistically significant (mean difference: 75 sec; 95% CI: -82 to 228 sec).


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)

Dextroamphetamine significantly decreases time to emergence from propofol anesthesia, but atomoxetine does not.(A) Rats received a bolus of propofol (8 mg/kg IV), followed by normal saline (vehicle), atomoxetine (1 mg/kg IV) or dextroamphetamine (1 mg/kg IV). Time to emergence was defined as the time from administration of propofol to return of righting. (B) Scatter plot of time to emergence for rats that received normal saline, dextroamphetamine, and atomoxetine after propofol. The lines represent mean values. Dextroamphetamine caused a statistically significant decrease in time to emergence compared to normal saline, whereas atomoxetine did not.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0131914.g002: Dextroamphetamine significantly decreases time to emergence from propofol anesthesia, but atomoxetine does not.(A) Rats received a bolus of propofol (8 mg/kg IV), followed by normal saline (vehicle), atomoxetine (1 mg/kg IV) or dextroamphetamine (1 mg/kg IV). Time to emergence was defined as the time from administration of propofol to return of righting. (B) Scatter plot of time to emergence for rats that received normal saline, dextroamphetamine, and atomoxetine after propofol. The lines represent mean values. Dextroamphetamine caused a statistically significant decrease in time to emergence compared to normal saline, whereas atomoxetine did not.
Mentions: Fig 2A shows the protocol for this experiment. Forty-five seconds after a single dose of propofol (8 mg/kg IV), normal saline (vehicle), dextroamphetamine (1 mg/kg IV) or atomoxetine (1 mg/kg IV) was administered, and time to emergence was recorded. Fig 2B shows a scatter plot of time to emergence after propofol for the normal saline, dextroamphetamine, and atomoxetine groups. The mean time to emergence for the normal saline group was 641 sec (95% CI: 530 to 759 sec, n = 8). In the dextroamphetamine group, mean time to emergence was 404 sec (95% CI: 371 to 439 sec, n = 8), and this reduction was statistically significant (mean difference: 237 sec; 95% CI: 121 to 358 sec). In the atomoxetine group, mean time to emergence was 566 sec (95% CI: 468 to 678 sec, n = 8) but this decrease in comparison to the normal saline group was not statistically significant (mean difference: 75 sec; 95% CI: -82 to 228 sec).

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