An endocannabinoid system is present in the mouse olfactory epithelium but does not modulate olfaction

Abstract

Endocannabinoids modulate a diverse array of functions including progenitor cell proliferation in the central nervous system, and odorant detection and food intake in the mammalian central olfactory system and larval Xenopus laevis peripheral olfactory system. However, the presence and role of endocannabinoids in the peripheral olfactory epithelium has not been examined in mammals. We found the presence of cannabinoid type 1 (CB1) and cannabinoid type 2 (CB2) receptor protein and mRNA in the olfactory epithelium. Using either immunohistochemistry or calcium imaging we localized CB1 receptors on neurons, glia like sustentacular cells, microvillous cells and progenitor-like basal cells. To examine the role of endocannabinoids, CB1 and CB2 receptor deficient (CB1−/−/CB2−/−) mice were used. The endocannabinoid 2-arachidonylglycerol (2-AG) was present at high levels in both C57BL/6 wildtype and CB1−/−/CB2−/− mice. 2-AG synthetic and degradative enzymes are expressed in wildtype mice. A small but significant decrease in basal cell and olfactory sensory neuron numbers was observed in CB1−/−/CB2−/− mice compared to wildtype mice. The decrease in olfactory sensory neurons did not translate to impairment in olfactory-mediated behaviors assessed by the buried food test and habituation/dishabituation test. Collectively, these data indicate the presence of an endocannabinoid system in the mouse olfactory epithelium. However, unlike in tadpoles, endocannabinoids do not modulate olfaction. Further investigation on the role of endocannabinoids in progenitor cell function in the olfactory epithelium is warranted.

Cannabis Users Show Enhanced Expression of CB1-5HT2A Receptor Heteromers in Olfactory Neuroepithelium Cells

“…Previous studies have shown that human ON cells exhibit a neuronal phenotype comprising several types of receptors including 5-HT 2C receptors and signaling pathways related to olfaction and other functional aspects of the CNS [16]. Likewise, expression of CB1R and the endocannabinoid, 2-arachidonylglycerol has been found in the ON of experimental animals [17,18]. Although alterations in CB1R levels have been described in the brain of cannabis users [19][20][21][22], and changes in endocannabinoid levels are detected in plasma following the administration of THC to healthy volunteers [23,24], no data has been provided yet regarding changes in 5HT2AR at central or peripheral level in this population.…”

Cannabinoid Control of Olfactory Processes: The Where Matters

“…Additionally, they found that the production of endocannabinoids depends on the hunger state of the animal, which is responsible for changes in odor sensitivity activity. Similarly, CB1 receptors were also found in the OSN of rodents [27]. The CB1 receptor agonists changed odorant-induced cellular activity, but the authors did not observe olfactory consequences in the behavior of mutant mice lacking CB1 receptors (CB1-KO; [27]).…”

“…Similarly, CB1 receptors were also found in the OSN of rodents [27]. The CB1 receptor agonists changed odorant-induced cellular activity, but the authors did not observe olfactory consequences in the behavior of mutant mice lacking CB1 receptors (CB1-KO; [27]). Despite the species differences, several divergences appear between these studies.…”

“…However, although relatively high levels of CB1 receptors were described in the 1990s in many olfactory brain areas of rodents [20][21][22][23], their olfactory-related functions only started to be studied during the last decade. Notably, the involvement of CB1 receptors in specific odor-related processes has been reported in specialized olfactory structures such as the olfactory epithelium (OE; [24][25][26][27]), the main olfactory bulb (MOB; [18,[28][29][30][31][32][33][34]), and the piriform cortex (PC; [35][36][37][38][39][40]), but also in other brain areas processing olfactory information [41][42][43][44]. For the sake of clarity in this review, we will focus on describing the role of the ECS, particularly CB1 receptor signaling, in specific main olfactory areas (i.e., OE, MOB, and PC).…”

“…For instance, the first two studies evaluated the impact of cannabinoids on odor sensitivity by recording the cellular activity of the OSN with calcium imaging and electrophysiological methods [24,25]. Instead, Hutch and colleagues [27] investigated the involvement of CB1 receptors in olfactory-mediated learning and memory tasks such as the buried food test and a habituation/dishabituation paradigm. In addition, CB1-KO mice lack brain specificity and might be confounded by compensatory mechanisms [49].…”