The role of nicotinic and muscarinic acetylcholine receptors in attention

Mirza, Naheed; Stolerman, I. P.

doi:10.1007/s002130050048

Cited by 99 publications

(78 citation statements)

References 41 publications

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“…The latter could be due to the higher dose used by Moore et al as also in the present study, the highest dose spared LI, or could reflect species differences (Moore et al used rabbits). The fact that scopolamine acts selectively in the PE groups, and that this action is exerted in the pre-exposure stage, implies that muscarinic blockade attenuates the normal loss of attention to the stimulus occurring during nonreinforced pre-exposure (Lubow et al, 1981), in line with extensive evidence implicating the cholinergic system in attentional processes (see Blokland, 1995;Hasselmo and McGaughy, 2004;Mirza and Stolerman, 2000;Sarter et al, 2003Sarter et al, , 1999Sarter et al, , 2005.…”

Section: Discussionmentioning

confidence: 65%

Scopolamine Induces Disruption of Latent Inhibition which is Prevented by Antipsychotic Drugs and an Acetylcholinesterase Inhibitor

Barak

Weiner

2006

Neuropsychopharmacol

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The fact that muscarinic antagonists may evoke a psychotic state ('antimuscarinic psychosis'), along with findings of cholinergic alterations in schizophrenia, have kindled an interest in the involvement of the cholinergic system in this disorder. Latent inhibition (LI) is a crossspecies phenomenon manifested as a poorer conditioning of a stimulus seen when the stage of conditioning is preceded by a stage of repeated nonreinforced pre-exposure to that stimulus, and is considered to index the capacity to ignore irrelevant stimuli. Amphetamine-induced LI disruption and its reversal by antipsychotic drugs (APDs) is a well-established model of positive symptoms of schizophrenia. Here, we tested whether the muscarinic antagonist scopolamine would disrupt LI and whether such disruption would be reversed by APDs and by the acetylcholinesterase inhibitor physostigmine. The results showed that scopolamine at doses of 0.15 and 0.5 mg/kg disrupted LI, and that this effect was due to the action of the drug in the pre-exposure stage, suggesting a role of muscarinic transmission in attentional processes underlying LI. Both the typical and the atypical APDs, haloperidol and clozapine, reversed scopolamine-induced LI disruption when given in conditioning or in both stages, but not in pre-exposure, indicating that the mechanism of antipsychotic action in this model is independent of the mechanism of action of the propsychotic drug. Scopolamine-induced LI disruption was reversed by physostigmine (0.05 and 0.15 mg/kg), which was ineffective in reversing amphetamine-induced LI disruption, pointing to distinct mechanisms underlying LI disruption by these two propsychotic drugs. The latter was further supported by the finding that unlike amphetamine, the LI-disrupting doses of scopolamine did not affect activity levels. We propose scopolamine-induced LI disruption as a model of cholinergic-related positive symptoms in schizophrenia. Neuropsychopharmacology (2007) 32, 989-999.

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Section: Discussionmentioning

confidence: 65%

Scopolamine Induces Disruption of Latent Inhibition which is Prevented by Antipsychotic Drugs and an Acetylcholinesterase Inhibitor

Barak

Weiner

2006

Neuropsychopharmacol

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“…The reason for the lack of effect of PQCA on reaction time compared with donepezil is unclear. Some evidence suggests that reaction time is influenced more by nicotinic receptors than by muscarinic receptors (Mirza and Stolerman, 2000). Thus, although donepezil's widespread effect on muscarinic and nicotinic receptors might be responsible for many of its adverse effects, donepezil's activation of nicotinic receptors might be beneficial for reaction time improvements.…”

Section: Pqca Improves Cognition In Rhesus Monkeysmentioning

confidence: 99%

The M1 Muscarinic Positive Allosteric Modulator PQCA Improves Performance on Translatable Tests of Memory and Attention in Rhesus Monkeys

Lange

Cannon

Drott

et al. 2015

J Pharmacol Exp Ther

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Improved treatment of Alzheimer disease (AD) is a significant unmet medical need that is becoming even more critical given the rise in the number of patients and the substantial economic burden. The current standards of care, acetylcholinesterase inhibitors (AChEIs), are hindered by gastrointestinal side effects owing to their nonselective activation of muscarinic and nicotinic receptors. Recently, the highly selective M1 positive allosteric modulator PQCA (1-((4-cyano-4-(pyridine-2-yl)piperidin-1-yl)methyl-4-oxo-4 H-quinolizine-3-carboxylic acid) has been demonstrated to improve cognition in a variety of rodent and nonhuman primate cognition models without producing significant gastrointestinal side effects. Here we describe the effect of PQCA and the AChEI donepezil on two clinically relevant and highly translatable touchscreen cognition tasks in nonhuman primates: paired-associates learning (PAL) and the continuous-performance task (CPT). Blockade of muscarinic signaling by scopolamine produced significant impairments in both PAL and CPT. PQCA and donepezil attenuated the scopolamine deficits in both tasks, and the action of these two compounds was similar in magnitude. In addition, the combination of subeffective doses of PQCA and donepezil enhanced PAL performance. These results further suggest that M1-positive allosteric modulators, either as monotherapy or as an add-on to current standards of care, have potential to reduce the cognitive deficits associated with AD.

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“…There is ample evidence that nAChR activation in general affects attention performance [4,7,40,41], but much less is known about the nAChR subtypes and brain areas involved. Several studies point to a specific role of cholinergic signalling in the medial prefrontal cortex and attention performance [9,17].…”

Section: Nicotinic Achrs In the Pfcmentioning

confidence: 99%

Nicotinic actions on neuronal networks for cognition: General principles and long-term consequences

Poorthuis

Goriounova

Couey

et al. 2009

Biochemical Pharmacology

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The role of nicotinic and muscarinic acetylcholine receptors in attention

Abstract: Both muscarinic and nicotinic cholinoceptors may be important in attention but they may serve different roles in information processing; this hypothesis could be tested using tasks that place different emphasis on different stages of information processing.

Cited by 99 publications

References 41 publications

Scopolamine Induces Disruption of Latent Inhibition which is Prevented by Antipsychotic Drugs and an Acetylcholinesterase Inhibitor

Scopolamine Induces Disruption of Latent Inhibition which is Prevented by Antipsychotic Drugs and an Acetylcholinesterase Inhibitor

The M1 Muscarinic Positive Allosteric Modulator PQCA Improves Performance on Translatable Tests of Memory and Attention in Rhesus Monkeys

Nicotinic actions on neuronal networks for cognition: General principles and long-term consequences

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