Abstract

Over the past decade, there has been increasing interest in the role of serotonin 6 (5-HT₆) receptors in higher cognitive processes such as memory. Polymorphisms of the 5-HT₆ receptor have been implicated in syndromes that affect cognition, such as schizophrenia and dementia. Manipulation of 5-HT₆ receptor activity alters the transmission of several neurotransmitters important in memory: acetylcholine and glutamate, as well as dopamine, ã-aminobutyric acid (GABA), epinephrine (E), and norepinephrine (NE). Several 5-HT₆ antagonists have been developed, advancing the understanding of the relationship between 5-HT₆ blockade and memory consolidation in diverse learning paradigms. There is also evidence that 5-HT₆ receptor activity affects anxiety behaviors and may be involved in the pathophysiology of schizophrenia. Several clinically useful atypical antipsychotics and antidepressants have 5-HT₆ affinity, but recently developed selective 5-HT₆ receptor antagonists may present attractive, new therapeutic options for several types of disease states.

Abbreviations: 5-HT, serotonin; 5,7-DHT, 5,7-dihydroxytryptamine; AO, antisense oligonucleotides; BDNF, brain derived growth factor; E, epinephrine; GABA, γ-aminobutyric acid; GAD, glutamic acid decarboxylase; GFP, green fluorescent protein; HSV, herpes simplex virus; LSD, lysergic acid diethylamide; MEST, maximal electroshock seizure threshold; NE, norepinephrine; NCAM, neural cell adhesion molecule; RT-PCR, reverse transcription polymerase chain reaction

Article Outline

1. 5-HT₆ receptor neurobiology

1.1. Introduction

1.2. Genetics

1.3. Pharmacology

2. 5-HT₆ interactions with other neurotransmitters

2.1. Acetylcholine

2.2. Dopamine

2.3. Excitatory amino acids

2.4. γ-Aminobutyric acid

2.5. Monoamines

3. Neurological disorders

3.1. Memory disorders/Alzheimer's disease

3.2. Anxiety/depression

3.3. Schizophrenia

3.4. Implications of 5-HT₆ interactions and cognition

4. Conclusion

Acknowledgements

References