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

Abstract

BACKGROUND AND PURPOSETransient 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 APPROACHWe investigated the role of TRPA1 in mice models of depression [forced swimming test (FST)] and anxiety [elevated plus maze (EPM) test]. KEY RESULTS Administration CONCLUSION AND IMPLICATIONSThe 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.

Transient Receptor Potential Channels as Drug Targets: From the Science of Basic Research to the Art of Medicine

“…In mice, the temperature sensitivity of the TRPA1 channel protein (cold vs. warm) is apparently determined by only three amino acid residues (Jabba et al, 2014); however, the native channel is not involved in autonomic thermoregulation (de Oliveira et al, 2014). It is noteworthy that TRPA1 blockade exerted an anxiolytic-like action in mice (de Moura et al, 2014). If this observation holds true in humans, TRPA1 antagonists (currently investigated in clinical trials as analgesics and cough-relieving drugs) may have an added clinical benefit.…”

Antidepressant activity of nociceptin/orphanin FQ receptor antagonists in the mouse learned helplessness

“…Only for the repeated fluoxetine administration, an extension of 72 h in the time frame between the screening session (session 2) and test session (session 3) was assumed. The dosages of nortriptyline and fluoxetine were based on previous studies demonstrating reversal of shock-induced shuttle box escape deficits after acute or repeated injections of these antidepressants (Telner et al 1981;Zazpe et al 2007) and decreased immobility in the forced swimming test (De Moura et al 2014;Da-Rocha et al 1997).…”

Spontaneous failure of the estrous cycle induces anxiogenic-related behaviors in middle-aged female mice

“…In a previous study from our research group, the effects of intraperitoneally (i.p.) injected diazepam 1 mg/kg, 15 min before the behavioral test were used for validating our experimental conditions [19]. Furthermore, the number of entries into closed arms was used as an index of general activity.…”

“…A mouse was judged to be immobile when it floated in an upright position, and made only small movements to keep its head above water. Previously, the effect of nortriptyline (a tricyclic antidepressant drug) orally injected 60 min before the test was evaluated [19]. The duration of immobility was recorded during the last 4 min of the 6-min testing time period.…”