The effect of pirenzepine on spatial learning in the Morris Water Maze

Hunter, A. J.; Roberts, F. F.

doi:10.1016/0091-3057(88)90490-x

Cited by 60 publications

(18 citation statements)

References 19 publications

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“…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. Moreover, the M 1 selective antagonists dicyclomine (Nilvebrant and Sparf, 1986) and S-(−)-ET-126 (Ghelardini et al, 1996) were able to induce amnesia in a mouse passive avoidance task (Ghelardini et al, 1997b;Matucci et al, 1997).…”

Section: Introductionmentioning

confidence: 98%

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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Section: Introductionmentioning

confidence: 98%

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

et al. 1999

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“…Such tests include passive (inhibitory) avoidance procedures, operant (matching and nonmatching) tasks, and spatial learning (and working memory) procedures such as water maze and radial arm maze tasks (reviewed, Decker and McGaugh, 1991). These data have been further extended to include selective muscarinic (i.e., M1) antagonists such as pirenzepine (Hunter and Roberts, 1988) as well as centrally acting nicotinic-cholinergic antagonists such as mecamylamine (Levin, 1992). Both muscarinic antagonists (Terry et al, 1993a;Vitiello et al, 1997) and nicotinic antagonists (Elrod and Buccafusco, 1991;Newhouse et al, 1994) have also been shown to impair memory performance in monkeys and humans.…”

Section: The Cholinergic Hypothesismentioning

confidence: 99%

The Cholinergic Hypothesis of Age and Alzheimer's Disease-Related Cognitive Deficits: Recent Challenges and Their Implications for Novel Drug Development

Terry

Buccafusco

2003

J Pharmacol Exp Ther

996

607

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The cholinergic hypothesis was initially presented over 20 years ago and suggests that a dysfunction of acetylcholine containing neurons in the brain contributes substantially to the cognitive decline observed in those with advanced age and Alzheimer's disease (AD). This premise has since served as the basis for the majority of treatment strategies and drug development approaches for AD to date. Recent studies of the brains of patients who had mild cognitive impairment or early stage AD in which choline acetyltransferase and/or acetylcholinesterase activity was unaffected (or even up-regulated) have, however, led some to challenge the validity of the hypothesis as well as the rationale for using cholinomimetics to treat the disorder, particularly in the earlier stages. These challenges, primarily based on assays of post mortem enzyme activity, should be taken in perspective and evaluated within the wide range of cholinergic abnormalities known to exist in both aging and AD. The results of both post mortem and antemortem studies in aged humans and AD patients, as well as animal experiments suggest that a host of cholinergic abnormalities including alterations in choline transport, acetylcholine release, nicotinic and muscarinic receptor expression, neurotrophin support, and perhaps axonal transport may all contribute to cognitive abnormalities in aging and AD. Cholinergic abnormalities may also contribute to noncognitive behavioral abnormalities as well as the deposition of toxic neuritic plaques in AD. Therefore, cholinergic-based strategies will likely remain valid as one approach to rational drug development for the treatment of AD other forms of dementia. The Cholinergic HypothesisA variety of studies in humans indicate that basal forebrain and rostral forebrain cholinergic pathways including converging projections to the thalamus serve important functional roles in conscious awareness, attention, working memory, and a number of additional mnemonic processes (Perry et al., 1999).For more than 20 years, studies of the brains of those with advanced age and Alzheimer's disease (AD) have consistently found damage or abnormalities in these pathways (particularly basal forebrain projections) that appeared to correlate well with the level of cognitive decline. As a result, the so-called "cholinergic hypothesis" was developed, which essentially states that a loss of cholinergic function in the central nervous system contributes significantly to the cognitive decline associated with advanced age and AD (reviewed, Bartus, 2000). Extensive literature from animal experiments supports the human data described above. In fact, the importance of cholinergic function in the brain to learning and memory was first recognized more than 30 years ago after cholinergic antagonists (specifically antimuscarinic agents) were found to impair memory in rats (Deutsch, 1971). Considerable additional evidence now supports this early work, and antimuscarinic agents such as scopolamine and atropine have been shown to impair memory

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“…It has been demonstrated that the M1 receptor subtype predominates in the cerebral cortex and hippocampus (Levey et al 1991;Wei et al 1994), areas in which cholinergic transmission appears to be essential to learning and memory processes. Moreover, blockade by the selective M1 receptor antagonist pirenzepine impairs learning of hippocampal-dependent tasks like delayed nonmatching to position (Aura et al 1997) and delayed matching to position (Andrews et al 1994) as well as working memory (Sala et al 1991), spatial memory (Hagan et al 1987;Hunter and Roberts 1988), and representational memory (Messer et al 1990) tests.…”

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confidence: 99%

Effects of the Selective M1 Muscarinic Receptor Antagonist Dicyclomine on Emotional Memory

Fornari¹,

Moreira²,

Oliveira³

2000

Learn. Mem.

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The nonselective muscarinic antagonist scopolamine is known to impair the acquisition of some learning tasks such as inhibitory avoidance. There has been recent research into the effects of this drug in contextual fear conditioning and tone fear conditioning paradigms. The purpose of the present study was to assess the role of the selective M1 muscarinic antagonist dicyclomine in these paradigms and in the inhibitory avoidance test. Rats were administered different doses of dicyclomine or saline 30 min before acquisition training. The animals were tested 24 hr later, and it was observed that 16 mg/kg of dicyclomine impaired both contextual fear conditioning and inhibitory avoidance. However, dicyclomine (up to 64 mg/kg) did not affect tone fear conditioning. These results suggest that the selective M1 muscarinic antagonist dicyclomine differentially affects aversively motivated tasks known to be dependent on hippocampal integrity (such as contextual fear conditioning and inhibitory avoidance) but does not affect similar hippocampus-independent tasks.

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The effect of pirenzepine on spatial learning in the Morris Water Maze

Cited by 60 publications

References 19 publications

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

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

The Cholinergic Hypothesis of Age and Alzheimer's Disease-Related Cognitive Deficits: Recent Challenges and Their Implications for Novel Drug Development

Effects of the Selective M1 Muscarinic Receptor Antagonist Dicyclomine on Emotional Memory

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