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Description
Over the past several decades, research on factors that influence alcohol consumption has focused primarily on the drug's post-ingestive effects. Self-administration of alcohol occurs naturally only via an oral route, yet research concerning how orosensory mechanisms mediate its consumption is limited. A better understanding of the mechanisms through which alcohol interacts with chemosensory circuits may facilitate the development of novel treatments for alcohol abuse. Alcohol is known to activate the trigeminal system, which is responsible for processing noxious stimuli. Recent findings have revealed that alcohol interacts with the trigeminal system in part through the TRPV1 receptor, a non-selective cation channel widely expressed in the oral mucosa that is activated by intense thermal and chemical stimuli. Data from our lab has shown that genetically engineered mice lacking the TRPV1 receptor exhibit reduced oral aversion to alcohol, indicating the TRPV1 receptor is involved in orosensory mediated alcohol avoidance. Although these mice display a significant reduction in oral ethanol avoidance compared to wild type controls, they maintain a concentration-dependent alcohol avoidance curve for concentrations above 5%, suggesting ethanol acts through other trigeminal mechanisms beyond the TRPV1 receptor. Prolonged exposure to capsaicin, a potent TRPV1 agonist, has been shown to be an effective method in desensitizing trigeminal afferent nerve fibers, reducing the sensitivity of these fibers to a wide variety of chemical trigeminal irritants (e.g. mustard oil, cinnamic aldehyde, etc.). The goal of the present study was to elucidate the role of the trigeminal system in orally-mediated responses to alcohol by inhibiting trigeminal sensitivity via local capsaicin desensitization of oral trigeminal nerve fibers. A brief access paradigm was utilized to measure short-term chemosensory responding to ethanol as well as prototypic sweet, bitter, and trigeminal stimuli in outbred Wistar rats. Psychophysical concentration-response functions were generated for each animal over the course of a three-day testing period on a given stimulus and used to assess differences in orosensory responding by treatment. Local oral capsaicin pretreatment effectively reduced chemosensory avoidance of capsaicin while leaving responding to gustatory stimuli (i.e. sucrose and quinine) unaffected. Furthermore, capsaicin-treated animals displayed a less pronounced concentration-dependent avoidance in sampling high ethanol concentrations relative to vehicle-treated controls, however, did not differ from vehicle-treated subjects in mean lick responses/trial or latency to initiate sampling for ethanol. The modest effects of local capsaicin desensitization on ethanol responding are in line with the previously observed reduction in ethanol avoidance resulting from knockout of the TRPV1 receptor, but suggest that the capsaicin dose employed may not have produced global inhibition of other trigeminal receptor subtypes potentially mediating aversive oral responses to ethanol. Alternative approaches are considered.
