Raised glucose levels enhance scopolamine-induced acetylcholine overflow from the hippocampus: an in vivo microdialysis study in the rat

Durkin, Thomas; Messier, Claude; Boer, P. de; Westerink, Ben H.C.

doi:10.1016/s0166-4328(05)80163-9

Cited by 97 publications

(43 citation statements)

References 34 publications

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“…During cognitive testing, which has been shown to enhance synaptic ACh (Giovannini et al, 1998;Dalley et al, 2001), an M 1 PAM such as MK-7622 would be expected to be much more potent relative to the less demanding cognitive state during resting qEEG recording. Furthermore, scopolamine increases extracellular ACh concentrations (Watanabe and Shimizu, 1989;Durkin et al, 1992), which could further contribute to the increased potency observed with MK-7622 in the scopolamine model. It is worth noting that the free concentrations of MK-7622 that were achieved in the brain, as reflected by total CSF levels, were likely not high enough to engender agonist activity on their own.…”

Section: Discussionmentioning

confidence: 99%

Preclinical to Human Translational Pharmacology of the Novel M₁ Positive Allosteric Modulator MK-7622

Uslaner¹,

Kuduk²,

Wittmann³

et al. 2018

J Pharmacol Exp Ther

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Section: Discussionmentioning

confidence: 99%

Preclinical to Human Translational Pharmacology of the Novel M₁ Positive Allosteric Modulator MK-7622

Uslaner¹,

Kuduk²,

Wittmann³

et al. 2018

J Pharmacol Exp Ther

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“…Moreover, the separation of muscarinic and nicotinic contributions is hampered by interactions between the receptors. For example, selectively blocking the muscarinic receptors by scopolamine, through blocking M2 presynaptic autoreceptors, induces a pronounced increase in ACh release, which, in turn, can lead to an overactivation of post-synaptic nicotinic receptors (Maviel and Durkin, 2003;Durkin et al, 1992). Thus, modeling the effects of a generally lowered cholinergic neurotransmission requires that both the cholinergic receptor types are blocked simultaneously, thereby avoiding increased nicotinic activation.…”

Section: Discussionmentioning

confidence: 99%

Impaired Off-Line Consolidation of Motor Memories After Combined Blockade of Cholinergic Receptors During REM Sleep-Rich Sleep

Rasch

Gais

Born

2009

Neuropsychopharmacol

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Rapid eye movement (REM) sleep has been considered important for the consolidation of memories, particularly of procedural skills. REM sleep, in contrast to slow-wave sleep (SWS), is hallmarked by the high, wake-like activity of the neurotransmitter acetylcholine (ACh), which promotes certain synaptic plastic processes underlying the formation of memories. Here, we show in healthy young men that off-line consolidation of a motor skill during a period of late sleep with high amounts of REM sleep depends essentially on high cholinergic activity. After a 3-h sleep period during the early night to satisfy the need for SWS, subjects learned a procedural finger sequence tapping task and a declarative word-pair learning task. After learning, they received either placebo or a combination of the muscarinic receptor antagonist scopolamine (4 mg/kg bodyweight, intravenously) and the nicotinic receptor antagonist mecamylamine (5 mg, orally), and then slept for another 3 h, ie, the late nocturnal sleep period, which is dominated by REM sleep. Retrieval was tested the following evening. Combined cholinergic receptor blockade significantly impaired motor skill consolidation, whereas word-pair memory remained unaffected. Additional data show that the impairing effect of cholinergic receptor blockade is specific to sleepdependent consolidation of motor skill and does not occur during a wake-retention interval. Taken together, these results identify high cholinergic activity during late, REM sleep-rich sleep as an essential factor promoting sleep-dependent consolidation of motor skills.

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“…Systemic glucose injections increase hippocampal ACh release (Durkin et al 1992), and both systemic and intrahippocampal glucose injections increase ACh release in the hippocampus while also enhancing spontaneous alternation performance (Ragozzino et al 1996(Ragozzino et al , 1998. Other putative memory-modulating mechanisms of glucose include regulation of potassium-ATP channels to modify neural excitability Gold 1998, 2001;Stefani et al 1999;Rashidy-Pour 2001), and modulation of GABA neurotransmission (Degroot et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Glucose injections into the dorsal hippocampus or dorsolateral striatum of rats prior to T-maze training: Modulation of learning rates and strategy selection

Canal¹,

Stutz²,

Gold³

2005

Learn. Mem.

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The present experiments examined the effects of injecting glucose into the dorsal hippocampus or dorsolateral striatum on learning rates and on strategy selection in rats trained on a T-maze that can be solved by using either a hippocampus-sensitive place or striatum-sensitive response strategy. Percentage strategy selection on a probe trial (P crit ) administered after rats achieved criterion (nine of 10 correct choices) varied by group. All groups predominately exhibited a response strategy on a probe trial administered after overtraining, i.e., after 90 trials. In experiment 1, rats that received intrahippocampal glucose injections showed enhanced acquisition of the T-maze and showed increased use of response solutions at P crit compared with that of unimplanted and artificial cerebral spinal fluid (aCSF)-treated groups. These findings suggest that glucose enhanced hippocampal functions to accelerate the rate of learning and the early adoption of a response strategy. In experiment 2, rats that received intrastriatal glucose injections exhibited place solutions early in training and reached criterion more slowly than did aCSF controls, with learning rates comparable to those of unoperated and operated-uninjected controls. Relative to unoperated, operated-uninjected and glucose-injected rats, rats that received intrastriatal aCSF injections showed enhanced acquisition of the T-maze and increased use of response solutions at P crit . The unexpected enhanced acquisition seen after striatal aCSF injections suggests at least two possible interpretations: (1) aCSF impaired striatal function, thereby releasing competition with the hippocampus and ceding control over learning to the hippocampus during early training trials; and (2) aCSF enhanced striatal functioning to facilitate striatal-sensitive learning. With either interpretation, the results indicate that intrastriatal glucose injections compensated for the aCSF-induced effect. Finally, enhanced acquisition regardless of treatment was accompanied by rapid adoption of a response solution for the T-maze.Glucose is a potent modulator of learning and memory for many tasks in both humans and rodents (Gold 1995(Gold , 2001 Korol and Gold 1998). For example, systemic administration of glucose enhances memory for verbal tasks in humans (cf. Gold 2001; Korol 2002;Benton et al. 2003;Messier 2004;Watson and Craft 2004) and enhances learning and memory in rats and mice for appetitive, aversive, operant, visual discrimination, spatial working memory, habituation, and extinction tasks (cf. Messier andWhite 1984, 1987; Gold 1986Gold , 1995Messier and Destrade 1988; Kopf and Baratti 1996;Messier 1997;Pavone et al. 1998;Ragozzino et al. 1998;Sansone et al. 2000;Talley et al. 2000;Benton et al. 2003; Hughes 2003;Schroeder and Packard 2003).In addition to the effects seen with systemic injections, glucose can also enhance learning and memory when injected directly into specific brain regions. Glucose injections into the medial septum or hippocampus modulate memory of spontaneou...

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Raised glucose levels enhance scopolamine-induced acetylcholine overflow from the hippocampus: an in vivo microdialysis study in the rat

Cited by 97 publications

References 34 publications

Preclinical to Human Translational Pharmacology of the Novel M₁ Positive Allosteric Modulator MK-7622

Preclinical to Human Translational Pharmacology of the Novel M₁ Positive Allosteric Modulator MK-7622

Impaired Off-Line Consolidation of Motor Memories After Combined Blockade of Cholinergic Receptors During REM Sleep-Rich Sleep

Glucose injections into the dorsal hippocampus or dorsolateral striatum of rats prior to T-maze training: Modulation of learning rates and strategy selection

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Raised glucose levels enhance scopolamine-induced acetylcholine overflow from the hippocampus: an in vivo microdialysis study in the rat

Cited by 97 publications

References 34 publications

Preclinical to Human Translational Pharmacology of the Novel M1 Positive Allosteric Modulator MK-7622

Preclinical to Human Translational Pharmacology of the Novel M1 Positive Allosteric Modulator MK-7622

Impaired Off-Line Consolidation of Motor Memories After Combined Blockade of Cholinergic Receptors During REM Sleep-Rich Sleep

Glucose injections into the dorsal hippocampus or dorsolateral striatum of rats prior to T-maze training: Modulation of learning rates and strategy selection

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Preclinical to Human Translational Pharmacology of the Novel M₁ Positive Allosteric Modulator MK-7622

Preclinical to Human Translational Pharmacology of the Novel M₁ Positive Allosteric Modulator MK-7622