Associate editor: B.L. Roth5-HT6 receptors: a novel target for cognitive enhancement
Section snippets
Acetylcholine
Acetylcholine is directly involved in anxiety, arousal, attention, fatigue, and sleep, as well as several memory processes such as acquisition and consolidation (Wood et al., 1978, Perry et al., 1999). The first recognition of 5-HT6 influence on acetylcholine was the observation of yawning, chewing, and stretching, as well as a reduction in locomotion, immediately following administration of a 5-HT6 antagonist, Ro 04-6790 (Bourson et al., 1995, Sleight et al., 1996). Bentley and colleagues
Memory disorders/Alzheimer's disease
As described in previous sections, Bentley et al. (1999) demonstrated that atropine, a muscarinic antagonist, blocked yawning and stretching behavior induced by 5-HT6 inhibition via antisense oligonucleotides (AO). This finding implied that other processes involving acetylcholine may be influenced by 5-HT6 activity. Because acetylcholine transmission is crucial for long-term memory formation, several groups focused on characterizing the effect of 5-HT6 inhibition in diverse learning paradigms.
Conclusion
In this review, emphasis has been placed on understanding 5-HT6 receptor effects on several groups of neurotransmitters and how these effects may translate into improved cognition during treatment of neurological disorders. Although many enlightening discoveries have been made in 5-HT6 genetics, pharmacology, and physiology, there are still conspicuous holes in our knowledge, such as the role of 5-HT6 receptors in development. Many research groups are in accordance over the pronounced influence
Acknowledgments
This work was supported by a NARSAD Independent Investigator Grant (to J.F.N.) and a NIA Genetic Basis of Aging Training Grant (to E.S.M.).
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2021, European Journal of Medicinal ChemistryCitation Excerpt :The spectrum of biological effects caused by the activation of 5-HT4R is very broad and relevant to the pathophysiology of AD, therefore addressing 5-HT4R is a commonly pursued strategy in the search for disease modifying-agents for AD [32–36]. Equally important is the serotonin receptor subtype 6 that is almost exclusively distributed in the brain areas involved in learning and memory processes [37–39] and several studies demonstrated a positive effect of the 5-HT6R antagonists on cognition [40–42]. In particular, the blockade of 5-HT6R was shown to increase acetylcholine levels and reverse cognition deficits induced by the administration of anticholinergic agents [43–45].