Kelsey Andreis
Advanced Summer Research Scholar
Major: Neuroscience
Mentor:Alex Straiker
Saliva serves multiple important functions within the body that we typically take for granted, such as helping prepare food for swallowing and defense against oral pathogens. Dry mouth is a primary symptom of Sjӧgren’s syndrome and is a side effect of many drug treatments. Cannabis users frequently report dry mouth, but the basis for this is still unknown. If the effects occur via the endogenous cannabinoid signaling system, then this may represent a novel mechanism for the regulation of salivation. We examined expression of cannabinoid CB1 receptors in submandibular salivary gland using immunohistochemistry and tested regulation of salivation by THC and cannabinoid-related ligands. We now report that CB1 receptors are expressed in the axons of neurons innervating the submandibular gland. No staining is seen in submandibular gland epithelial cells (acinar and ductal), or myoepithelial cells (MECs). Treatment with THC (4mg/kg, IP) or the cannabinoid receptor agonist CP55940 (0.5mg/kg) reduced salivation in both male and female mice one hour after treatment. The CB1 receptor antagonist SR141716 (4mg/kg) had no effect on salivation. The CB2-selective agonist JWH133 (4mg/kg) had no effect on salivation. In addition, we tested knockout mice for FAAH, the
enzyme that metabolizes the endocannabinoid anandamide. We found that salivation was reduced in males and females. Interestingly, treatment with the FAAH blocker URB597 (4mg/kg) only reduced salivation in males. This may be an indication of sex-dependence or that more time is required to see an effect in females. The most parsimonious explanation for our findings is that THC lowers salivation by activating CB1 receptors on neurons that innervate the salivary glands. Our results also implicate anandamide as the endogenous cannabinoid messenger mediating these effects.
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