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, 30nmol in 2μL, i.c.v.) reduced immobility time in the FST. Similar results were obtained after oral administration of HC030031 (30-300mg·kg-1). The reduction in immobility time in FST induced by HC030031 (100mg·kg-1) was completely prevented by pretreatment with TRPA1 agonist, cinnamaldehyde (50mg·kg-1, p.o.), which per se was inactive. In the EPM test, pretreatment with cinnamaldehyde (50mg·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, 100mg·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. © 2014 The British Pharmacological Society.

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

PRETI, Delia;Geppetti, Pierangelo;Gavioli, Elaine Cristina
Penultimo
;
2014

Abstract

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, 30nmol in 2μL, i.c.v.) reduced immobility time in the FST. Similar results were obtained after oral administration of HC030031 (30-300mg·kg-1). The reduction in immobility time in FST induced by HC030031 (100mg·kg-1) was completely prevented by pretreatment with TRPA1 agonist, cinnamaldehyde (50mg·kg-1, p.o.), which per se was inactive. In the EPM test, pretreatment with cinnamaldehyde (50mg·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, 100mg·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. © 2014 The British Pharmacological Society.
de 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
File in questo prodotto:
File Dimensione Formato  
bph12786.pdf

accesso aperto

Descrizione: versione editoriale
Tipologia: Full text (versione editoriale)
Licenza: PUBBLICO - Pubblico con Copyright
Dimensione 875.85 kB
Formato Adobe PDF
875.85 kB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2329464
Citazioni
  • ???jsp.display-item.citation.pmc??? 12
  • Scopus 32
  • ???jsp.display-item.citation.isi??? 30
social impact