In vivo effects of propofol on acetylcholine release from the frontal cortex, hippocampus and striatum studied by intracerebral microdialysis in freely moving rats

Kikuchi, Takayuki; Wang, Y; Sato, Kazuo; Okumura, Fukuichiro

doi:10.1093/bja/80.5.644

Cited by 63 publications

(31 citation statements)

References 21 publications

(13 reference statements)

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“…The decrease in habituated learning observed in the present study may be due to changes in local signaling networks, as increased GABAergic firing inhibits cholinergic interneuron activity (DeBoer and Westerink, 1994;Kikuchi et al, 1998), which has been shown to be integral to instrumental learning (Ragozzino, 2003). Alternatively, 5-HT 6 overexpression may be inhibiting learning primarily through direct and indirect basal ganglia pathways (Graybiel, 1986).…”

Section: Discussionmentioning

confidence: 71%

Increased Expression of 5-HT6 Receptors in the Rat Dorsomedial Striatum Impairs Instrumental Learning

Mitchell

Sexton

Neumaier

2006

Neuropsychopharmacol

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A number of studies have shown that systemic 5-HT 6 receptor antagonists can improve learning and memory, but the mechanism for these observations is not known. As striatum normally expresses 5-HT 6 receptors abundantly and is important in consolidating stimulusresponse learning, we used targeted gene delivery to further increase the expression of 5-HT 6 receptors in rat striatum and then examined learning. Increased 5-HT 6 expression had no effect on performance in the Morris water maze, a hippocampal-dependent learning paradigm, and did not alter the latency to approach or consume sucrose tablets. However, rats with increased 5-HT 6 expression failed to acquire a reward-based instrumental learning task, a striatum-dependent learning model, during 3 days of successive sessions as compared to sham surgery or GFP-expressing control rats. This behavioral deficit was observed in rats overexpressing 5-HT 6 receptors in the dorsomedial striatum, but not in rats with increased dorsocentral striatal expression. The 5-HT 6 receptor-associated deficit was reversed by administration of a 5-HT 6 antagonist, SB-258585, before each training session. When animals learned the instrumental learning task before gene transfer, increased 5-HT 6 receptor expression had no effect on long-term recall or performance of the task or on extinction of operant responding. Thus, 5-HT 6 receptor activity in rat striatum disrupts acquisition of new instrumental learning but does not impair memory or performance of reward-motivated behavior once established.

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Section: Discussionmentioning

confidence: 71%

Increased Expression of 5-HT6 Receptors in the Rat Dorsomedial Striatum Impairs Instrumental Learning

Mitchell

Sexton

Neumaier

2006

Neuropsychopharmacol

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“…Multiple lines of evidence suggest that propofol also acts by reducing the action of ACh and HA. Indeed, propofol is shown to decrease the level of ACh in frontal cortex (Kikuchi et al, 1998) and to attenuate ACh receptor responses (Flood et al, 1997; Murasaki et al, 2003). Increasing ACh transmission prevents the action of propofol in humans (Meuret et al, 2000).…”

Section: Resultsmentioning

confidence: 99%

Cellular and neurochemical basis of sleep stages in the thalamocortical network

Krishnan

Chauvette

Shamie

et al. 2016

eLife

116

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The link between the combined action of neuromodulators in the brain and global brain states remains a mystery. In this study, using biophysically realistic models of the thalamocortical network, we identified the critical intrinsic and synaptic mechanisms, associated with the putative action of acetylcholine (ACh), GABA and monoamines, which lead to transitions between primary brain vigilance states (waking, non-rapid eye movement sleep [NREM] and REM sleep) within an ultradian cycle. Using ECoG recordings from humans and LFP recordings from cats and mice, we found that during NREM sleep the power of spindle and delta oscillations is negatively correlated in humans and positively correlated in animal recordings. We explained this discrepancy by the differences in the relative level of ACh. Overall, our study revealed the critical intrinsic and synaptic mechanisms through which different neuromodulators acting in combination result in characteristic brain EEG rhythms and transitions between sleep stages.DOI: http://dx.doi.org/10.7554/eLife.18607.001

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“…For example, propofol administration to rats decreases cortical acetylcholine release, and, in human volunteers, propofol-induced unconsciousness can be reversed with physostigmine [35,36]. The hypnotic effects of adenosine injected into the medial preoptic area are blocked by flumazenil [37].…”

Section: Discussionmentioning

confidence: 99%