Serotonin and anxiety (WP2141)

Mus musculus

Benekareddy et al observed the phenomenon that rats who were maternally separated show increased levels of induced anxiety-related behaviour during adulthood. Type 2 serotonin receptors have been implicated in anxiety related behaviour and may be suitable targets for reducing anxiety response. Benekareddy et al report that treatment with ketanserin (a serotonergic antagonist) during postnatal life blocked the long-lasting effects of maternal separation on anxiety behavior in the open field test and the elevated plus maze. Immediate Early Genes such as Arc have been found to be significantly affected in expression (Benekareddy et al). The downstream and upstream gene products of Arc were partly elucidated and presented in a pathway.


Helix , Onne Ronda , Andra Waagmeester , Daniela Digles , Egon Willighagen , Martina Summer-Kutmon , Kristina Hanspers , and Denise Slenter


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Mus musculus



Pathway Ontology

serotonin signaling pathway altered calcineurin signaling pathway calcium/calmodulin dependent kinase signaling pathway

Disease Ontology

anxiety disorder

Cell Type Ontology

serotonergic neuron


Label Type Compact URI Comment
THDOC Metabolite pubchem.compound:91475
Ketanserin Metabolite pubchem.compound:3822
Ca2+ Metabolite chebi:29108
Ca2+ Metabolite chebi:29108
Ca2+ Metabolite chebi:29108
DOC Metabolite pubchem.compound:6166
Plcd4 GeneProduct ensembl:ENSMUSG00000026173
Plek GeneProduct ensembl:ENSMUSG00000020120 pleckstrin
Pomc GeneProduct ensembl:ENSMUSG00000020660
mGluR1 GeneProduct ensembl:ENSMUSG00000019828 G-protein-coupled phosphatidylinositol-calcium second messenger system
Trpv1 GeneProduct ensembl:ENSMUSG00000005952
Prkcb GeneProduct ensembl:ENSMUSG00000052889 Protein kinase C
CaM GeneProduct ensembl:ENSMUSG00000057897
Fmr1 GeneProduct ensembl:ENSMUSG00000000838
eEF2K GeneProduct ensembl:ENSMUSG00000073853
Crh GeneProduct ensembl:ENSMUSG00000049796
Ppp3ca GeneProduct ensembl:ENSMUSG00000028161 calcineurin
eEF2-P GeneProduct uniprot:P58252
Gabra1 GeneProduct ensembl:ENSMUSG00000010803 GABA a receptor
eEF2K GeneProduct ensembl:ENSMUSG00000073853 Phosphorylates eEF2
Arc GeneProduct ensembl:ENSMUSG00000022602 Calcium ion channel
Htr2c GeneProduct ensembl:ENSMUSG00000041380
Fos GeneProduct ensembl:ENSMUSG00000021250
Htr1a GeneProduct ensembl:ENSMUSG00000021721
Adra1a GeneProduct ensembl:ENSMUSG00000045875
Arc GeneProduct ensembl:ENSMUSG00000022602
eEF2 GeneProduct uniprot:P58252
Htr2a GeneProduct ensembl:ENSMUSG00000034997
mGluR1 GeneProduct ensembl:ENSMUSG00000019828 G-protein-coupled phosphatidylinositol-calcium second messenger system
eEF2-P GeneProduct uniprot:P58252
Arc GeneProduct ensembl:ENSMUSG00000022602


  1. The alpha-adrenergic receptor blocking effect of ketanserin and the interaction between alpha-adrenergic and S2-serotonergic receptor blockade. van der Starre PJ, Reneman RS. J Cardiovasc Pharmacol. 1988;11 Suppl 1:S54-61. PubMed Europe PMC Scholia
  2. ARC channels: a novel pathway for receptor-activated calcium entry. Shuttleworth TJ, Thompson JL, Mignen O. Physiology (Bethesda). 2004 Dec;19:355–61. PubMed Europe PMC Scholia
  3. Physiological role of adrenal deoxycorticosterone-derived neuroactive steroids in stress-sensitive conditions. Reddy DS. Neuroscience. 2006;138(3):911–20. PubMed Europe PMC Scholia
  4. The immediate early gene arc/arg3.1: regulation, mechanisms, and function. Bramham CR, Worley PF, Moore MJ, Guzowski JF. J Neurosci. 2008 Nov 12;28(46):11760–7. PubMed Europe PMC Scholia
  5. Postnatal serotonin type 2 receptor blockade prevents the emergence of anxiety behavior, dysregulated stress-induced immediate early gene responses, and specific transcriptional changes that arise following early life stress. Benekareddy M, Vadodaria KC, Nair AR, Vaidya VA. Biol Psychiatry. 2011 Dec 1;70(11):1024–32. PubMed Europe PMC Scholia
  6. Calcineurin is required for TRPV1-induced long-term depression of hippocampal interneurons. Jensen T, Edwards JG. Neurosci Lett. 2012 Feb 29;510(2):82–7. PubMed Europe PMC Scholia