Brain Circuits Regulated by the 5-HT2A Receptor: Behavioural Consequences on Anxiety and Fear Memory

  • L. Moulédous
  • P. Roullet
  • Bruno P. Guiard
Part of the The Receptors book series (REC, volume 32)


Anxiety disorders including generalized anxiety disorder (GAD), panic disorder (PD), social anxiety disorder (SAD) or phobias are the most prevalent mental pathologies across the world with a median lifetime prevalence of approximately 15%. Anxiety imposes substantial economic costs which are among the highest of all mental disorders studied. Evidence is now accumulating that the serotonergic nervous system is involved in the pathology of anxiety and can provide benefits in the treatment of related disorders through its diverse functions, notably the modulation of stress, fear and memory. Among serotonin receptor subtypes, the 5-HT2A receptor arouses great interest. This receptor displays original pharmacological properties i.e., cooperation with β-arrestins and homo−/hetero-dimerization regulating its intracellular signaling and its ability to control the serotonergic system. The present chapter provides insight into the mechanisms by which the 5-HT2A receptor may alter the activity of 5-HT neurons but also of the brain regions receiving a dense serotonergic innervation (i.e, the amygdala, the hippocampus and the prefrontal cortex). An overview of the literature is proposed to recapitulate the pharmacological and genetic studies in patients or relevant animal models supporting a role of the 5-HT2A receptor on various forms of anxiety. Moreover, we envision the future directions that we might follow to develop new anxiolytic strategies based on the manipulation of 5-HT2A-mediated signaling. Doing so, we also point some inconsistencies illustrating the difficulty to target this receptor as a valid alternative to benzodiazepines.


5-HT2A receptor Amygdala Animal studies Anxiety Fear memory Hippocampus Monoaminergic circuits 





5-Hydroxytryptamine 2A




Brain-derived neurotrophic factor


Basolateral complex of amygdala


Central nucleus of amygdala


Corticotropin releasing factor


Corticotropin releasing factor receptor








Dentate gyrus


Dorsal raphe


Elevated plus maze


Extracellular signal-regulated kinase


Elevated T-maze


Four plate test


Generalized anxiety disorders


Granule cell


Glial cell line-derived neurotrophic factor




Inositol Triphosphate


Inhibitory post-synaptic currents


Locus coeruleus


Lysergic acid diethylamide


Medial amygdala


Medial prefrontal cortex


Median raphe




Novelty suppressed feeding


Open field


Object in Context Recognition Task


Periaqueducal grey


Panic disorders


Protein kinase C


Phospholipase C




Social anxiety disorder


Subgranular zone


Spontaneous Novel Object Recognition task


Single nucleotide polymorphism




Serotonin selective reuptake inhibitors


Tonic immobility


Temporal Order Recognition Task


Tryptophan hydroxylase


Vascular endothelial growth factor


Ventral tegmental area


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© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Research Center on Animal Cognition, Center for Integrative BiologyUniversité Paul Sabatier, UMR 5169 CNRSToulouse Cedex 9France
  2. 2.Faculté de Pharmacie, Université Paris SudUniversité Paris-SaclayChatenay-MalabryFrance
  3. 3.Centre de Recherches sur la Cognition Animale (CRCA), Centre de Biologie Intégrative (CBI)Université de Toulouse; CNRS, UPSToulouseFrance

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