In:
British Journal of Pharmacology, Wiley, Vol. 171, No. 18 ( 2014-09), p. 4289-4299
Abstract:
Transient receptor potential vanilloid 1 ( TRPV 1) and TRP ankyrin 1 ( TRPA 1) are involved in many biological processes, including nociception and hyperalgesia. Whereas the involvement of TRPV 1 in psychiatric disorders such as anxiety and depression has been reported, little is known regarding the role of TRPA 1 in these conditions. Experimental Approach We investigated the role of TRPA 1 in mice models of depression [forced swimming test ( FST )] and anxiety [elevated plus maze (EPM) test ]. Key Results Administration of the TRPA 1 antagonist ( HC 030031, 30 nmol in 2 μL, i.c.v.) reduced immobility time in the FST . Similar results were obtained after oral administration of HC 030031 (30–300 mg·kg −1 ). The reduction in immobility time in FST induced by HC 030031 (100 mg·kg −1 ) was completely prevented by pretreatment with TRPA 1 agonist, cinnamaldehyde (50 mg·kg −1 , p.o.), which per se was inactive. I n 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 TRPA 1 blockade ( HC 030031, 100 mg·kg −1 , p.o.). Treatment with either cinnamaldehyde or HC 030031 did not affect spontaneous ambulation. Furthermore, TRPA 1‐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 TRPA 1 produces inhibitory activity in mouse models of anxiety and depression. These results imply that TRPA 1 exerts tonic control, promoting anxiety and depression, and that TRPA 1 antagonism has potential as an innovative strategy for the treatment of anxiety and mood disorders.
Type of Medium:
Online Resource
ISSN:
0007-1188
,
1476-5381
DOI:
10.1111/bph.2014.171.issue-18
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2029728-2
SSG:
15,3
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