Abstract
In addition to positive and negative symptoms, cognitive deficits are increasingly being recognized as a core feature of schizophrenia. Neurocognitive impairments are strongly associated with functional outcomes; thus, the treatment of cognitive impairments is of central importance. A large body of evidence suggests that the serotonin 6 (5-HT6) receptors may be potential targets for cognitive improvement. Clinical and preclinical studies have supported the notion that using 5-HT6 receptor antagonists is a promising component in the treatment of cognitive dysfunctions associated with aging and Alzheimer’s disease. However, less is known about the efficacy of this strategy in the treatment of schizophrenia-like cognitive disturbances. The purpose of this review is to summarize existing data on the effects of 5-HT6 receptor antagonists in animal experiments, utilizing tasks that assess cognitive domains that are relevant to the cognitive deficits characterizing schizophrenia. This review focuses primarily on animal models of schizophrenia that are based on the blockade of N-methyl-d-aspartate receptors; however, when relevant, data obtained in other models are also discussed. The putative procognitive actions of 5-HT6 agonists are also reviewed. Finally, the mechanisms that are putatively responsible for the procognitive effects of 5-HT6 receptor ligands are briefly discussed.
Acknowledgments
This study was supported by the Statutory Funds of the Institute of Pharmacology, Polish Academy of Sciences and project ‘Prokog’, UDA-POIG.01.03.01-12-063/09-00, co-financed by the European Union from the European Fund of Regional Development (EFRD).
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Articles in the same Issue
- Frontmatter
- Guest Editorial
- Special issue: potential therapeutic targets involving 5-HT6 and 5-HT7 receptors
- Reviews
- Serotonergic 5-HT7 receptors and cognition
- Memory formation and memory alterations: 5-HT6 and 5-HT7 receptors, novel alternative
- Molecular imaging of the serotonin 5-HT7 receptors: from autoradiography to positron emission tomography
- The procognitive effects of 5-HT6 receptor ligands in animal models of schizophrenia
- Modulatory effects following subchronic stimulation of brain 5-HT7-R system in mice and rats
- Selective agonists for serotonin 7 (5-HT7) receptor and their applications in preclinical models: an overview
- 5-HT6 receptor antagonists as treatment for age-related cognitive decline
- The role of serotonin 5-HT7 receptor in regulating sleep and wakefulness
- Novel insights into the potential involvement of 5-HT7 receptors in endocrine dysregulation in stress-related disorders
- Computational approaches to the design of novel 5-HT6 R ligands
Articles in the same Issue
- Frontmatter
- Guest Editorial
- Special issue: potential therapeutic targets involving 5-HT6 and 5-HT7 receptors
- Reviews
- Serotonergic 5-HT7 receptors and cognition
- Memory formation and memory alterations: 5-HT6 and 5-HT7 receptors, novel alternative
- Molecular imaging of the serotonin 5-HT7 receptors: from autoradiography to positron emission tomography
- The procognitive effects of 5-HT6 receptor ligands in animal models of schizophrenia
- Modulatory effects following subchronic stimulation of brain 5-HT7-R system in mice and rats
- Selective agonists for serotonin 7 (5-HT7) receptor and their applications in preclinical models: an overview
- 5-HT6 receptor antagonists as treatment for age-related cognitive decline
- The role of serotonin 5-HT7 receptor in regulating sleep and wakefulness
- Novel insights into the potential involvement of 5-HT7 receptors in endocrine dysregulation in stress-related disorders
- Computational approaches to the design of novel 5-HT6 R ligands