Involvement of TRPV1 in the Olfactory Bulb in Rimonabant-Induced Olfactory Discrimination Deficit

10.4077/CJP.2016.BAE366

Sherry Shu-Jung Hu

cannabinoids ； capsazepine ； CB_1 knockout mice ； CB_1 receptors ； olfactory bulb ； olfactory functions ； TRPV1

The Chinese Journal of Physiology

59卷1期（2016 / 02 / 29）

21 - 32

英文

Rimonabant is well recognized as a cannabinoid CB_1 receptor antagonist/inverse agonist. Rimonabant not only antagonizes the effects induced by exogenous cannabinoids and endocannabinoids at CB_1 receptors, it also exerts several pharmacological and behavioral effects independent of CB_1 receptor inactivation. For example, rimonabant can function as a low-potency mixed agonist/antagonist of the transient receptor potential vanilloid receptor 1 (TRPV1). Hence, it is important to explain the underlying mechanisms of the diverse physiological effects induced by rimonabant with caution. Interestingly, CB_1 receptor has recently been suggested to play a role in olfactory functions. Olfaction not only is involved in food intake, visual perception and social interaction, but also is proposed as a putative marker for schizophrenia and autism. Therefore, the present study aimed to investigate whether CB_1 receptor and TRPV1 played a role in olfactory functions. We first used the genetic disruption approach to examine the role of CB_1 receptor in olfactory functions and found that CB_1 knockout mice exhibited olfactory discrimination deficit. However, it is important to point out that these CB_1 knockout mice, despite their normal locomotivity, displayed deficiencies in the olfactory foraging and novel object exploration tasks. These results imply that general exploratory behaviors toward odorant and odorless objects are compromised in CB_1 knockout mice. We next turned to the pharmacological approach to examine the role of CB_1 receptor and TRPV1 in olfactory functions. We found that the short-term administration of rimonabant, injected systemically or directly into the olfactory bulb (OB), impaired olfactory discrimination that was rescued by the TRPV1 antagonist capsazepine (CPZ), via the same route of rimonabant, in wild-type mice. These results suggest that TRPV1 in the OB is involved in rimonabant-induced olfactory discrimination deficit. However, the rimonabant and/or CPZ treatments neither affected locomotivity nor general exploratory behaviors in wild-type mice. Finally, the acute systemic administration of rimonabant, unlike the short-term administration regimen, did not affect olfactory discrimination. Taken together, this study not only is the first one, to the best of our knowledge, suggests that the olfactory TRPV1 plays a role in olfactory functions, but also provides a possible mechanism for the olfactory discrimination deficit induced by rimonabant.

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