Hdl Handle:
http://hdl.handle.net/10675.2/125
Title:
Role of the central cholinergic system in the therapeutics of schizophrenia.
Authors:
Terry, Alvin V.
Abstract:
The therapeutic agents currently used to treat schizophrenia effectively improve psychotic symptoms; however, they are limited by adverse effects and poor efficacy when negative symptoms of the illness and cognitive dysfunction are considered. While optimal pharmacotherapy would directly target the neuropathology of schizophrenia neither the underlying neurobiological substrates of the behavioral symptoms nor the cognitive deficits have been clearly established. Abnormalities in the neurotransmitters dopamine, serotonin, glutamate, and GABA are commonly implicated in schizophrenia; however, it is not uncommon for alterations in the brain cholinergic system (e.g., choline acetyltransferase, nicotinic and muscarinic acetylcholine receptors) to also be reported. Further, there is now considerable evidence in the animal literature to suggest that both first and second generation antipsychotics (when administered chronically) can alter the levels of several cholinergic markers in the brain as well as impair memory-related task performance. Given the well-established importance of central cholinergic neurons to information processing and cognition, it is important that cholinergic function in schizophrenia be further elucidated and that the mechanisms of the chronic effects of antipsychotic drugs on this important neurotransmitter system be identified. A better understanding of these mechanisms would be expected to facilitate optimal treatment strategies for schizophrenia as well as the identification of novel therapeutic targets. In this review, the following topics are discussed: 1) the central cholinergic system in schizophrenia 2) effects of antipsychotic drugs on central cholinergic neurons 3) important neurotrophins in schizophrenia, especially those that support central cholinergic neurons; 4) novel strategies to optimize the therapeutics of schizophrenia via the use of cholinergic compounds as primary (i.e., antipsychotic) treatments as well as adjunctive, pro-cognitive agents.
Citation:
Curr Neuropharmacol. 2008 Sep; 6(3):286-292
Issue Date:
9-Jun-2009
URI:
http://hdl.handle.net/10675.2/125
DOI:
10.2174/157015908785777247
PubMed ID:
19506725
PubMed Central ID:
PMC2687934
Type:
Journal Article
ISSN:
1570-159X
Appears in Collections:
Department of Pharmacology and Toxicology: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorTerry, Alvin V.en_US
dc.date.accessioned2010-09-24T22:03:24Z-
dc.date.available2010-09-24T22:03:24Z-
dc.date.issued2009-06-09en_US
dc.identifier.citationCurr Neuropharmacol. 2008 Sep; 6(3):286-292en_US
dc.identifier.issn1570-159Xen_US
dc.identifier.pmid19506725en_US
dc.identifier.doi10.2174/157015908785777247en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/125-
dc.description.abstractThe therapeutic agents currently used to treat schizophrenia effectively improve psychotic symptoms; however, they are limited by adverse effects and poor efficacy when negative symptoms of the illness and cognitive dysfunction are considered. While optimal pharmacotherapy would directly target the neuropathology of schizophrenia neither the underlying neurobiological substrates of the behavioral symptoms nor the cognitive deficits have been clearly established. Abnormalities in the neurotransmitters dopamine, serotonin, glutamate, and GABA are commonly implicated in schizophrenia; however, it is not uncommon for alterations in the brain cholinergic system (e.g., choline acetyltransferase, nicotinic and muscarinic acetylcholine receptors) to also be reported. Further, there is now considerable evidence in the animal literature to suggest that both first and second generation antipsychotics (when administered chronically) can alter the levels of several cholinergic markers in the brain as well as impair memory-related task performance. Given the well-established importance of central cholinergic neurons to information processing and cognition, it is important that cholinergic function in schizophrenia be further elucidated and that the mechanisms of the chronic effects of antipsychotic drugs on this important neurotransmitter system be identified. A better understanding of these mechanisms would be expected to facilitate optimal treatment strategies for schizophrenia as well as the identification of novel therapeutic targets. In this review, the following topics are discussed: 1) the central cholinergic system in schizophrenia 2) effects of antipsychotic drugs on central cholinergic neurons 3) important neurotrophins in schizophrenia, especially those that support central cholinergic neurons; 4) novel strategies to optimize the therapeutics of schizophrenia via the use of cholinergic compounds as primary (i.e., antipsychotic) treatments as well as adjunctive, pro-cognitive agents.en_US
dc.rightsThe PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset.en_US
dc.titleRole of the central cholinergic system in the therapeutics of schizophrenia.en_US
dc.typeJournal Articleen_US
dc.identifier.pmcidPMC2687934en_US
dc.contributor.corporatenameDepartment of Pharmacology and Toxicologyen_US
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