The Cholinergic Synapse and the Site of Memory

Deutsch, J. A.

doi:10.1007/978-1-4684-3060-8_11

Cited by 489 publications

(126 citation statements)

References 18 publications

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“…In addition, at higher doses AChE inhibitors might 'overstimulate' ACh receptor systems in the brain. Thus, adequate performance of PA retention seems to depend on an optimal level of cholinergic receptor stimulation (Deutsch, 1971). This means that a delicate balance between pre-and postsynaptic ACh receptor mechanisms is probably required to compete with the functional muscarinic receptor blockade caused by the high-affinity receptor antagonist scopolamine.…”

Section: Discussionmentioning

confidence: 99%

Selective 5-HT1A Antagonists WAY 100635 and NAD-299 Attenuate the Impairment of Passive Avoidance Caused by Scopolamine in the Rat

Misane

Ögren

2003

Neuropsychopharmacol

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Systemic administration of the muscarinic-receptor antagonists atropine and scopolamine produces cognitive deficits in humans, nonhuman primates and rodents. In humans, these deficits resemble symptoms of dementia seen in Alzheimer's disease. The passive avoidance (PA) task has been one of the most frequently used animal models for studying cholinergic mechanisms in learning and memory. The present study examined the ability of two selective 5-HT 1A receptor antagonists WAY 100635 and NAD-299 (robalzotan) and two acetylcholinesterase (AChE) inhibitors tacrine and donepezil to attenuate the impairment of PA retention caused by the nonselective muscarinic receptor antagonist scopolamine in the rat. Although demonstrating differences in their temporal kinetics, both WAY 100635 and NAD-299 attenuated the impairment of PA caused by scopolamine (0.3 mg/kg s.c.). Donepezil did not block the PA deficit caused by the 0.3 mg/kg dose of scopolamine, but it prevented the inhibitory effects of the 0.2 mg/kg dose of scopolamine. In contrast, tacrine was effective vs both the 0.2 and 0.3 mg/kg doses of scopolamine. These results indicate that (1) a functional 5-HT 1A receptor antagonism can attenuate the anterograde amnesia produced by muscarinic-receptor blockade, and (2) the AChE inhibitors tacrine and donepezil differ in their ability to modify muscarinic-receptor-mediated function in vivo. These results suggest that 5-HT 1A receptor antagonists may have a potential in the treatment of cognitive symptoms in psychopathologies characterized by reduced ACh transmission such as Alzheimer's disease.

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Section: Discussionmentioning

confidence: 99%

Selective 5-HT1A Antagonists WAY 100635 and NAD-299 Attenuate the Impairment of Passive Avoidance Caused by Scopolamine in the Rat

Misane

Ögren

2003

Neuropsychopharmacol

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“…Thus, targeting pharmacological treatments to the CNS without affecting the peripheral functions of acetylcholine has been a difficult challenge. In understanding the function of acetylcholine in the brain, a special emphasis has been placed on the importance of acetylcholine for memory and learning 26,27 with a focus on a specific role of the cholinergic forebrain system in attention. 21,28 A deficit in the function of the cholinergic system is thus likely to result in cognitive impairment.…”

Section: Cholinergic Neurotransmissionmentioning

confidence: 99%

Towards a muscarinic hypothesis of schizophrenia

Raedler

Bymaster

Tandon³

et al. 2006

Mol Psychiatry

247

211

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Although the neurotransmitter dopamine plays a prominent role in the pathogenesis and treatment of schizophrenia, the dopamine hypothesis of schizophrenia fails to explain all aspects of this disorder. It is increasingly evident that the pathology of schizophrenia also involves other neurotransmitter systems. Data from many streams of research including preclinical and clinical pharmacology, treatment studies, post-mortem studies and neuroimaging suggest an important role for the muscarinic cholinergic system in the pathophysiology of schizophrenia. This review will focus on evidence that supports the hypothesis that the muscarinic system is involved in the pathogenesis of schizophrenia and that muscarinic receptors may represent promising novel targets for the treatment of this disorder.

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“…On the other hand, cholinergic blockade produces significant impairments of cognitive functions. A delay-dependent disruption following treatment with scopolamine and atropine, that appeared to resemble that occurring spontaneously in aged subjects and in Alzheimer patients, has been reported (Duetsch, 1971;Bartus and Johnson, 1976). Animals treated with the M 1 selective antagonist pirenzepine (Hammer et al, 1980), had impaired passive avoidance learning (in mice) (Caufield et al, 1983) and impaired spatial learning (Hagan et al, 1987;Hunter and Roberts, 1988), radial arm maze performance (Sala et al, 1991) and active avoidance acquisition (Sen and Bhattacharya, 1991) in rats.…”

Section: Introductionmentioning

confidence: 97%

Antisense ‘knockdowns’ of M1 receptors induces transient anterograde amnesia in mice

et al. 1999

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The effect on memory processes of inactivation of the M 1 gene by an antisense oligodeoxyribonucleotide (aODN) was investigated in the mouse passive avoidance test. Mice received a single intracerebroventricular (i.c.v.) injection of M 1 aODN (0.3, 1.0 or 2.0 nmol per injection), degenerated ODN (dODN) or vehicle on days 1, 4 and 7. An amnesic effect, comparable to that produced by antimuscarinic drugs, was observed 12, 24, 48 and 72 h after the last i.c.v. aODN injection, whereas dODN and vehicle, used as controls, did not produce any effect. Reduction in the entrance latency to the dark compartment induced by aODN disappeared 7 days after the end of aODN treatment, which indicates the absence of any irreversible damage or toxicity caused by aODN. Quantitative reverse transcription-polymerase chain reaction analysis demonstrated that a decrease in M 1 mRNA levels occurred only in the aODN-treated group, being absent in all control groups. Furthermore, a reduction in M 1 receptors was observed in the hippocampus of aODN-treated mice. Neither aODN, dODN nor vehicle produced any behavioral impairment of mice. These results indicate that the integrity and functionality of M 1 receptors are fundamental in the modulation of memory processes.

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The Cholinergic Synapse and the Site of Memory

Cited by 489 publications

References 18 publications

Selective 5-HT1A Antagonists WAY 100635 and NAD-299 Attenuate the Impairment of Passive Avoidance Caused by Scopolamine in the Rat

Selective 5-HT1A Antagonists WAY 100635 and NAD-299 Attenuate the Impairment of Passive Avoidance Caused by Scopolamine in the Rat

Towards a muscarinic hypothesis of schizophrenia

Antisense ‘knockdowns’ of M1 receptors induces transient anterograde amnesia in mice

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