5-HT system and cognition
Neuroscience & Biobehavioral ReviewsPublished 1 December 1999
A. Meneses
Citations470
SJR quartileQ1
SJR score3.08
SNIP2.62
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TL;DR
Available evidence strongly suggests that the 5-HT system may be important in normal function, the treatment and/or pathogenesis of cognitive disorders, and selective drugs with agonists, neutral antagonist, agonists or inverse agonist properties could constitute a new therapeutic opportunity for learning and memory alterations.
Abstract
The study of 5-hydroxytryptamine (5-HT) system has benefited from the identification, classification and cloning of multiple 5-HT receptors (5-HT1 to 5-HT7). Growing evidence suggests that 5-HT is important in learning and memory and all its receptors might be implicated in this. Actually, 5-HT pathways, 5-HT reuptake site/transporter complex and 5-HT receptors show regional distribution in brain areas implicated in learning and memory. Likewise, the stimulation or blockade of presynaptic 5-HT1A, 5-HT1B, 5-HT(2A/2C) and 5-HT3 receptors, postsynaptic 5-HT(2B/2C) and 5-HT4 receptors and 5-HT uptake/transporter sites modulate these processes. Available evidence strongly suggests that the 5-HT system may be important in normal function, the treatment and/or pathogenesis of cognitive disorders. Further investigation will help to specify the 5-HT system nature involvement in cognitive processes, pharmacotherapies, their mechanisms and action sites and to determine under which conditions they could operate. In this regard, it is probable that selective drugs with agonists, neutral antagonist, agonists or inverse agonist properties for 5-HT1A, 5-HT(1B/1D), 5-HT(2A/2B/2C), 5-HT4 and 5-HT7 receptors could constitute a new therapeutic opportunity for learning and memory alterations.
Keywords
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Trends in Pharmacological SciencesThe structure and signalling properties of 5-HT receptors: an endless diversity?
57 Citations1998G.R Martin
It became evident during the course of the symposium that receptor isoforms produced by alternative splicing or mRNA editing will need to be embraced by the NC-IUPHAR scheme, yet criteria by which to judge whether these isoforms are functional, or merely the result of `leaky transcription', remain to be established.
Neurobiology of Learning and Memory5-HT1AReceptors Modulate the Consolidation of Learning in Normal and Cognitively Impaired Rats
56 Citations1999Alfredo Meneses, Enrique Hong
Data confirm a role for presynaptic 5-HT1A receptors during the consolidation of learning and support the hypothesis that serotonergic, cholinergic, and glutamatergic systems interact in cognitively impaired animals.
British Journal of PharmacologyAnalysis of the 5‐HT<sub>1A</sub>receptor involvement in passive avoidance in the rat
54 Citations1998Ilga Misane, Christina Johansson +1 more
The findings indicate that the deficit of passive avoidance retention induced by the 5‐HT1A agonists is mainly a result of stimulation of postsynaptic 5‐ HT1A receptors but not5‐HT2A receptors, which appears to interfere with learning processes operating at both acquisition and retrieval.
Journal of Pharmacology and Experimental TherapeuticsLY215840, a high-affinity 5-HT7 receptor ligand, blocks serotonin-induced relaxation in canine coronary artery.
54 Citations1996D J Cushing, J M Zgombick +2 more
The ability of LY215840 to block the relaxant 5- HT receptor in canine coronary artery may reflect its 5-HT7 receptor antagonist activity and make it a useful tool to probe the relationship between the 5-Hat7 receptor and the coronary vasoactive properties of 5-ht.
Drug Development ResearchAnimal models of dementia
54 Citations1995Roger D. Porsolt, Sylvain Roux +1 more
The aging animal would appear to represent the best available model providing it can be shown that the cognitive deficits observed are similar to those observed in old age in humans.
Behavioural Brain ResearchEffects of the 5-HT receptor antagonists GR127935 (5-HT1B/1D) and MDL100907 (5-HT2A) in the consolidation of learning
53 Citations1997Alfredo Meneses, José A Terrón +1 more
The present findings suggest that stimulation of presynaptic 5-HT1B/1D receptors impairs the consolidation of learning whilst stimulation of5-HT2A/2C receptors enhances it; the blockade of 5- HT2A receptors has no effects.
NeuropsychobiologyCognition and Vigilance: Differential Effects of Diazepam and Buspirone on Memory and Psychomotor Performance
51 Citations2008Agnieszka Unrug-Neervoort, Gilles van Luijtelaar +1 more
Results indicate that effects of anxiolytics on memory can be more easily demonstrated 1 week later than immediately after drug intake and, furthermore, that the disruptive effects of diazepam outweight the small effects of buspirone.
Blackwell Scientific eBooksCentral serotonin receptors and psychotropic drugs
51 Citations1992C.A. Marsden, David J. Heal
Part I: Classification of 5- HT Receptor Subtypes in the Central Nervous System 5-HT receptor binding sites in the central nervous system and their distribution Neurochemical identification of 5,HT receptor subtypes Central 5-ht receptor sub types: physiological responses and signal transduction mechanisms Pharmacological identification of5-HT receptors subtypes using behavioural models 5-Hat receptor distribution in the human brain: autoradiographic studies
HippocampusChanges in exploratory activity following stimulation of hippocampal 5‐HT1A and 5‐HT1B receptors in the rat
50 Citations1995Marie‐Christine Buhot, Saïd Naïli
The hypothesis of the involvement of the serotonergic system, via 5HT1A and 5‐HT1B receptors, in the modulation of hippocampal functions is supported.
Behavioural Brain ResearchRole of 5-HT1B, 5-HT2A and 5-HT2C receptors in learning
50 Citations1997Alfredo Meneses, Enrique Hong
The present data suggest that both 5-HT1B and5-HT2A-2C receptors play a significant role in the consolidation of learning and are likely to reflect activation of postsynaptic receptors.
European Journal of Pharmacology5-HT1A and muscarinic acetylcholine receptors jointly regulate passive avoidance behavior
49 Citations1994Paavo Riekkinen
The present data suggest that behavioral defect caused by hypostimulation of muscarinic acetylcholine receptors is aggravated by concurrent 5-HT1A receptor stimulation.
PsychopharmacologyComparison of the effects of the 5-HT3 receptor antagonists WAY-100579 and ondansetron on spatial learning in the water maze in rats with excitotoxic lesions of the forebrain cholinergic projection system
49 Citations1996Helen Hodges, Piotr Sowiński +2 more
Results are consistent with previous studies which demonstrated that another selective 5-HT3 receptor antagonist, WAY-100289, significantly reversed the cognitive deficits in water maze performance induced by ibotenic acid lesions of forebrain cholinergic projection system.
Brain Research5-HT 1A agonists induce hippocampal theta activity in freely moving cats: role of presynaptic 5-HT 1A receptors
47 Citations1996F Marrosu, Casimir A. Fornal +2 more
The results suggest that preferential activation of presynaptic 5-HT1A receptors, and subsequent inhibition of serotonin neurotransmission, facilitates the appearance of hippocampal theta activity in awake cats.
SynapseAutoregulatory properties of dorsal raphe 5-HT neurons: Possible role of electrotonic coupling and 5-HT1D receptors in the rat brain
47 Citations1996Graciela Pi�eyro, Claude de Montigny +2 more
The testing of the hypothesis that somatodendritic availability of 5‐hydroxytryptamine (5‐HT) could be regulated independently of the firing activity of dorsal raphe 5‐HT neurons suggested the existence of electrotonic coupling of 5-HT neurons, and indicated that 5‐ HT release in the rat dorsal Raphe nucleus may be controlled independently of firing‐regulating 5‐ht1A autoreceptors.
Mechanisms of Ageing and DevelopmentAge-related changes in septal serotonergic, GABAergic and glutamatergic facilitation of retention in SAMP8 mice
46 Citations1998James F. Flood, Susan A. Farr +2 more
This study determined if altered functional status of neurotransmission in the septum might account for the decrease in cholinergic and glutamatergic activity in the hippocampus of older SAMP8 mice, which may show an age-related impairment of septohippocampal functioning.
PsychopharmacologyEffects of serotonin 5-HT 2A/2C antagonists on associative learning in the rabbit
45 Citations1998Sarah E Welsh, Anthony G. Romano +1 more
The ability of ritanserin and MDL-11,939 to produce effects on learning and performance that were opposite to that of 5-HT2A/2C agonists suggests that they may be acting as inverse agonists at that receptor.
Neurobiology of Learning and MemoryChicks Injected with Antisera to either S-100α or S-100β Protein Develop Amnesia for a Passive Avoidance Task
44 Citations1997Brona S. O'Dowd, Wei Zhao +2 more
It is concluded that the two subunits of the S-100 protein are required at different points in the sequence of events leading to the consolidation of passive avoidance memory.
Journal of NeurochemistryAntisense Oligonucleotide‐Induced Reduction in 5‐Hydroxytryptamine<sub>7</sub> Receptors in the Rat Hypothalamus Without Alteration in Exploratory Behaviour or Neuroendocrine Function
43 Citations1998Delyth A Clemett, Mark I. Cockett +2 more
The results suggest that this antisense protocol could be a valuable tool to investigate central 5‐HT7 receptor functions, and that this receptor is not critical for the control of neuroendocrine function or food intake.
European Journal of Pharmacology5-HT1A receptor agonists induce anterograde amnesia in mice through a postsynaptic mechanism
41 Citations1993Scott D. Mendelson, David Quartermain +2 more
It is concluded that 5-HT1A receptor agonists and partial agonists produce a reversible anterograde amnesia that is mediated by postsynaptic 5- HT1A receptors.
Drug Development ResearchPharmacological studies of a rat spatial delayed nonmatch‐to‐sample task as an animal model of dementia
40 Citations1991Robert Michael John Deacon
A variation of the delayed nonmatch‐to‐sample task in rats has recently been described in which the spatial positions of retractable levers are used as the sample and response cues, and selectivity encourages the development of this model or similar models in the search for compounds with the potential to treat dementia.
Journal of Pharmacology and Experimental TherapeuticsFull and Partial 5-HT1A Receptor Agonists Disrupt Learning and Performance in Rats
37 Citations1999Peter J. Winsauer, Floréal Rodriguez +2 more
The results indicate that complex behaviors in rats are sensitive to disruption by drugs with both full and partial 5-HT1A receptor agonist properties, and that the effects of partial 5.HT1a receptor agonists on learning may be different depending on their efficacy at pre- and postsynaptic 5- HT1A receptors.
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