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The blockade of transient receptor potential ankirin 1 ( TRPA 1) signalling mediates antidepressant‐ and anxiolytic‐like actions in mice
Author(s) -
Moura Juliana Cavalcante,
Noroes Maíra Macedo,
Rachetti Vanessa de Paula Soares,
Soares Bruno Lobão,
Preti Delia,
Nassini Romina,
Materazzi Serena,
Marone Ilaria Maddalena,
Minocci Daiana,
Geppetti Pierangelo,
Gavioli Elaine Cristina,
André Eunice
Publication year - 2014
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12786
Subject(s) - transient receptor potential channel , chemistry , behavioural despair test , pharmacology , anxiolytic , trpm8 , agonist , medicine , endocrinology , biochemistry , antidepressant , receptor , trpv1 , hippocampus
Background and Purpose 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.