Increased noradrenaline release from rat preoptic area during and after sevoflurane and isoflurane anesthesia

Anzawa, Noriyuki; Kushikata, Tetsuya; Ohkawa, Hirobumi; Yoshida, Hitoshi; Kubota, Takeshi; Matsuki, Akitomo

doi:10.1007/bf03028309

Cited by 27 publications

(18 citation statements)

References 23 publications

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“…First, compared with the awake condition, isoflurane evokes a substantial three- to fourfold increase of noradrenaline in the rat preoptic area. 39 However, as the duration of the microdialysis was only 50 minutes, it is not a simple matter to predict whether noradrenaline release remains stable or declines with the prolonged anesthesia used in the present study. When we consider the possibility that the effect of isoflurane on the level of noradrenaline could be constant, we would expect an underestimation of the BP ND in both the baseline and inhibition states, compared with an awake state.…”

Section: Discussionmentioning

confidence: 90%

Quantification of [¹¹C]yohimbine Binding to α₂ Adrenoceptors in Rat Brain in vivo

Phan

Landau

Wong

et al. 2015

J Cereb Blood Flow Metab

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We quantified the binding potentials (BPND) of [11C]yohimbine binding in rat brain to alpha-2 adrenoceptors to evaluate [11C]yohimbine as an in vivo marker of noradrenergic neurotransmission and to examine its sensitivity to the level of noradrenaline. Dual [11C]yohimbine dynamic positron emission tomography (PET) recordings were applied to five Sprague Dawley rats at baseline, followed by acute amphetamine administration (2 mg/kg) to induce elevation of the endogenous level of noradrenaline. The volume of distribution (VT) of [11C]yohimbine was obtained using Logan plot with arterial plasma input. Because alpha-2 adrenoceptors are distributed throughout the brain, the estimation of the BPND is complicated by the absence of an anatomic region of no displaceable binding. We used the Inhibition plot to acquire the reference volume, VND, from which we calculated the BPND. Acute pharmacological challenge with amphetamine induced a significant decline of [11C]yohimbine BPND of ~38% in all volumes of interest. The BPND was greatest in the thalamus and striatum, followed in descending order by, frontal cortex, pons, and cerebellum. The experimental data demonstrate that [11C]yohimbine binding is sensitive to a challenge known to increase the extracellular level of noradrenaline, which can benefit future PET investigations of pathologic conditions related to disrupted noradrenergic neurotransmission.

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Section: Discussionmentioning

confidence: 90%

Quantification of [¹¹C]yohimbine Binding to α₂ Adrenoceptors in Rat Brain in vivo

Phan

Landau

Wong

et al. 2015

J Cereb Blood Flow Metab

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“…The effects of isoflurane on LC neurons and NE are not as clear cut as those of dexmedetomidine. Though isoflurane has been shown to depress LC activity (this effect is most pronounced during the night cycle where LC neurons are most active) 39 ; rats anesthetized with 2% isoflurane show increases in POA norepinephrine 40 . Given the divergent effects of dexmedetomidine and isoflurane on norepinephrine, we expected enhanced glymphatic transport with DEXM-I anesthesia compared with isoflurane only anesthesia.…”

Section: Discussionmentioning

confidence: 99%

Anesthesia with Dexmedetomidine and Low-dose Isoflurane Increases Solute Transport via the Glymphatic Pathway in Rat Brain When Compared with High-dose Isoflurane

et al. 2017

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Background The glymphatic pathway transports cerebrospinal fluid through the brain, thereby facilitating waste removal. A unique aspect of this pathway is that its function depends on the state of consciousness of the brain and is associated with norepinephrine activity. A current view is that all anesthetics will increase glymphatic transport by inducing unconsciousness. This view implies that the effect of anesthetics on glymphatic transport should be independent of their mechanism of action, as long as they induce unconsciousness. We tested this hypothesis by comparing the supplementary effect of dexmedetomidine, which lowers norepinephrine, with isoflurane only, which does not. Methods Female rats were anesthetized with either isoflurane (N = 8) or dexmedetomidine plus low-dose isoflurane (N = 8). Physiologic parameters were recorded continuously. Glymphatic transport was quantified by contrast-enhanced magnetic resonance imaging. Cerebrospinal fluid and gray and white matter volumes were quantified from T1 maps, and blood vessel diameters were extracted from time-of-flight magnetic resonance angiograms. Electroencephalograms were recorded in separate groups of rats. Results Glymphatic transport was enhanced by 32% in rats anesthetized with dexmedetomidine plus low-dose isoflurane when compared with isoflurane. In the hippocampus, glymphatic clearance was sixfold more efficient during dexmedetomidine plus low-dose isoflurane anesthesia when compared with isoflurane. The respiratory and blood gas status was comparable in rats anesthetized with the two different anesthesia regimens. In the dexmedetomidine plus low-dose isoflurane rats, spindle oscillations (9 to 15 Hz) could be observed but not in isoflurane anesthetized rats. Conclusions We propose that anesthetics affect the glymphatic pathway transport not simply by inducing unconsciousness but also by additional mechanisms, one of which is the repression of norepinephrine release.

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“…During emergence from sevoflurane and isoflurane, microdialysis studies confirm surges in norepinephrine in the preoptic area of the hypothalamus. 31 Within basal forebrain, norepinephrine can directly promote transient arousals. 32 If released upon sleep-active ventrolateral preoptic hypothalamus (VLPO) and median preoptic hypothalamic neurons, norepinephrine’s hyperpolarizing actions should inhibit activity in these groups, which would release inhibition of other wake-active systems, thus enhancing arousal.…”

Section: Discussionmentioning

confidence: 99%

Hypnotic Hypersensitivity to Volatile Anesthetics and Dexmedetomidine in Dopamine β-Hydroxylase Knockout Mice

Hanna

Han

et al. 2012

Anesthesiology

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BACKGROUND Multiple lines of evidence suggest that the adrenergic system can modulate sensitivity to anesthetic-induced immobility and anesthetic-induced hypnosis as well. However, several considerations prevent the conclusion that the endogenous adrenergic ligands norepinephrine and epinephrine alter anesthetic sensitivity. METHODS Using dopamine β-hydroxylase (Dbh−/−) mice genetically engineered to lack the adrenergic ligands and their siblings with normal adrenergic levels, we test the contribution of the adrenergic ligands upon volatile anesthetic induction and emergence. Moreover, we investigate the effects of intravenous dexmedetomidine in adrenergic-deficient mice and their siblings using both righting reflex and processed electroencephalographic measures of anesthetic hypnosis. RESULTS We demonstrate that the loss of norepinephrine and epinephrine and not other neuromodulators copackaged in adrenergic neurons is sufficient to cause hypersensitivity to induction of volatile anesthesia. However, the most profound effect of adrenergic deficiency is retarding emergence from anesthesia, which takes two to three times as long in Dbh−/− mice for sevoflurane, isoflurane, and halothane. Having shown that Dbh−/− mice are hypersensitive to volatile anesthetics, we further demonstrate that their hypnotic hypersensitivity persists at multiple doses of dexmedetomidine. Dbh−/− mice exhibit up to 67% shorter latencies to loss of righting reflex and up to 545% longer durations of dexmedetomidine-induced general anesthesia. Central rescue of adrenergic signaling restores control-like dexmedetomidine sensitivity. A novel continuous electroencephalographic analysis illustrates that the longer duration of dexmedetomidine-induced hypnosis is not due to a motor confound, but occurs because of impaired anesthetic emergence. CONCLUSIONS Adrenergic signaling is essential for normal emergence from general anesthesia. Dexmedetomidine-induced general anesthesia does not depend upon inhibition of adrenergic neurotransmission.

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Increased noradrenaline release from rat preoptic area during and after sevoflurane and isoflurane anesthesia

Cited by 27 publications

References 23 publications

Quantification of [¹¹C]yohimbine Binding to α₂ Adrenoceptors in Rat Brain in vivo

Quantification of [¹¹C]yohimbine Binding to α₂ Adrenoceptors in Rat Brain in vivo

Anesthesia with Dexmedetomidine and Low-dose Isoflurane Increases Solute Transport via the Glymphatic Pathway in Rat Brain When Compared with High-dose Isoflurane

Hypnotic Hypersensitivity to Volatile Anesthetics and Dexmedetomidine in Dopamine β-Hydroxylase Knockout Mice

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Increased noradrenaline release from rat preoptic area during and after sevoflurane and isoflurane anesthesia

Cited by 27 publications

References 23 publications

Quantification of [11C]yohimbine Binding to α2 Adrenoceptors in Rat Brain in vivo

Quantification of [11C]yohimbine Binding to α2 Adrenoceptors in Rat Brain in vivo

Anesthesia with Dexmedetomidine and Low-dose Isoflurane Increases Solute Transport via the Glymphatic Pathway in Rat Brain When Compared with High-dose Isoflurane

Hypnotic Hypersensitivity to Volatile Anesthetics and Dexmedetomidine in Dopamine β-Hydroxylase Knockout Mice

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Quantification of [¹¹C]yohimbine Binding to α₂ Adrenoceptors in Rat Brain in vivo

Quantification of [¹¹C]yohimbine Binding to α₂ Adrenoceptors in Rat Brain in vivo