The blockade of transient receptor potential ankirin 1 (TRPA1) signalling mediates antidepressant- and anxiolytic-like actions in mice

Br J Pharmacol. 2014 Sep;171(18):4289-99. doi: 10.1111/bph.12786.


Background and purpose: Transient receptor potential vanilloid 1 (TRPV1) and TRP ankyrin 1 (TRPA1) are involved in many biological processes, including nociception and hyperalgesia. Whereas the involvement of TRPV1 in psychiatric disorders such as anxiety and depression has been reported, little is known regarding the role of TRPA1 in these conditions.

Experimental approach: We investigated the role of TRPA1 in mice models of depression [forced swimming test (FST)] and anxiety [elevated plus maze (EPM) test].

Key results: Administration of the TRPA1 antagonist (HC030031, 30 nmol in 2 μL, i.c.v.) reduced immobility time in the FST. Similar results were obtained after oral administration of HC030031 (30-300 mg·kg(-1) ). The reduction in immobility time in FST induced by HC030031 (100 mg·kg(-1) ) was completely prevented by pretreatment with TRPA1 agonist, cinnamaldehyde (50 mg·kg(-1) , p.o.), which per se was inactive. In the EPM test, pretreatment with cinnamaldehyde (50 mg·kg(-1) , p.o.), which per se did not affect behaviour response, prevented the anxiolytic-like effect (increased open arm exploration) evoked by TRPA1 blockade (HC030031, 100 mg·kg(-1) , p.o.). Treatment with either cinnamaldehyde or HC030031 did not affect spontaneous ambulation. Furthermore, TRPA1-deficient mice showed anxiolytic- and antidepressant-like phenotypes in the FST and EPM test respectively.

Conclusion and implications: The present findings indicate that genetic deletion or pharmacological blockade of TRPA1 produces inhibitory activity in mouse models of anxiety and depression. These results imply that TRPA1 exerts tonic control, promoting anxiety and depression, and that TRPA1 antagonism has potential as an innovative strategy for the treatment of anxiety and mood disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetanilides / pharmacology
  • Acrolein / analogs & derivatives
  • Acrolein / pharmacology
  • Animals
  • Anti-Anxiety Agents / pharmacology
  • Antidepressive Agents / pharmacology
  • Anxiety / physiopathology*
  • Behavior, Animal
  • Depression / physiopathology*
  • Diazepam / pharmacology
  • Disease Models, Animal
  • Male
  • Mice, Knockout
  • Nortriptyline / pharmacology
  • Purines / pharmacology
  • Signal Transduction
  • Swimming
  • TRPA1 Cation Channel
  • Transient Receptor Potential Channels / antagonists & inhibitors
  • Transient Receptor Potential Channels / genetics
  • Transient Receptor Potential Channels / physiology*


  • 2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide
  • Acetanilides
  • Anti-Anxiety Agents
  • Antidepressive Agents
  • Purines
  • TRPA1 Cation Channel
  • Transient Receptor Potential Channels
  • Trpa1 protein, mouse
  • Acrolein
  • Nortriptyline
  • Diazepam
  • cinnamaldehyde