lithium-chloride and Dysgeusia

Oral mucositis and taste dysfunction are frequently complained by patients with head and neck cancer receiving radiotherapy, challenging the clinical outcome of cancer treatment. Recent studies have indicated the protective role of Wnt/β-catenin signaling in radiation-induced oral mucositis (RIOM) and its pivotal role in the development and self-renewal of taste buds. The current study hypothesizes that lithium chloride (LiCl), a potent activator of the Wnt/β-catenin signaling pathway, can promote the postirradiation restoration of oral mucosa integrity and taste function. To validate this hypothesis, we established a RIOM mouse model and evaluated the treatment efficacy of LiCl on oral mucositis and taste dysfunction in comparison with keratinocyte growth factor (KGF), an agent approved by the US Food and Drug Administration for oral mucositis. The results showed that LiCl alleviated the weight loss and tongue ulceration of RIOM mice, promoted proliferation of basal epithelial cells, and inhibited epithelial-mesenchymal transition in tongue mucosa. More important, elevated taste bud renewal and dysgeusia recovery toward sweetness were observed in RIOM mice treated with LiCl as compared to those treated by KGF. Collectively, our data demonstrate that LiCl can mitigate oral mucositis and rescue taste alteration induced by irradiation, and activation of Wnt/β-catenin signaling may represent a promising therapy to improve the quality of life of patients receiving radiotherapy.

Topics: Animals; Dysgeusia; Humans; Lithium Chloride; Mice; Quality of Life; Stomatitis; Wnt Signaling Pathway

Voluntary running in an activity wheel establishes aversion to paired taste in rats. A proposed mechanism underlying this taste aversion learning is gastrointestinal discomfort caused by running. We tested this hypothesis by measuring the pica behavior (kaolin clay intake) of rats, because it is known that rats engage in pica behavior after various nausea-inducing treatments including irradiation, motion sickness, and injection of emetic drugs such as lithium chloride (LiCl). Following a demonstration of the already-known phenomenon of LiCl-based pica in Experiment 1, we successfully showed running-based pica behavior in Experiment 2 where the running treatment was compared with a non-running control treatment (i.e., confinement in a locked wheel). These results suggest that not only LiCl but also running induces nausea in rats, supporting the gastrointestinal discomfort hypothesis of running-based taste aversion learning.

Topics: Abdominal Pain; Aluminum Silicates; Animals; Avoidance Learning; Behavior, Animal; Clay; Disease Models, Animal; Dysgeusia; Emetics; Injections, Intraperitoneal; Kaolin; Lithium Chloride; Male; Models, Biological; Motor Activity; Nausea; Physical Exertion; Pica; Rats, Wistar; Stress, Physiological

Previously, published studies have reported mixed results regarding the role of the TRPM5 cation channel in signaling sweet taste by taste sensory cells. Some studies have reported a complete loss of sweet taste preference in TRPM5 knockout (KO) mice, whereas others have reported only a partial loss of sweet taste preference. This study reports the results of conditioned aversion studies designed to motivate wild-type (WT) and KO mice to respond to sweet substances. In conditioned taste aversion experiments, WT mice showed nearly complete LiCl-induced response suppression to sucrose and SC45647. In contrast, TRPM5 KO mice showed a much smaller conditioned aversion to either sweet substance, suggesting a compromised, but not absent, ability to detect sweet taste. A subsequent conditioned flavor aversion experiment was conducted to determine if TRPM5 KO mice were impaired in their ability to learn a conditioned aversion. In this experiment, KO and WT mice were conditioned to a mixture of SC45647 and amyl acetate (an odor cue). Although WT mice avoided both components of the stimulus mixture, they avoided SC45647 more than the odor cue. The KO mice also avoided both stimuli, but they avoided the odor component more than SC45647, suggesting that while the KO mice are capable of learning an aversion, to them the odor cue was more salient than the taste cue. Collectively, these findings suggest the TRPM5 KO mice have some residual ability to detect SC45647 and sucrose, and, like bitter, there may be a TRPM5-independent transduction pathway for detecting these substances.

Topics: Animals; Choice Behavior; Conditioning, Psychological; Dysgeusia; Guanidines; Lithium Chloride; Mice; Mice, Knockout; Odorants; Pentanols; Signal Transduction; Smell; Sucrose; Sweetening Agents; Taste; Taste Perception; TRPM Cation Channels

N-methyl-D-aspartate (NMDA) receptor antagonists are often used to assess the role of NMDA receptors in learning and memory processes. However, few studies have explored the possibility that the antagonists may induce a conditioned aversion when administered following flavor consumption. We report five experiments with rats intended to evaluate the MK-801 capacity to induce conditioned taste aversion. Our findings suggest that: i) MK-801 produces a low-intensity aversion following repeated pairings with saccharin (Experiments 1 and 2); ii) such aversion was not the result of a non-associative process (Experiment 3); and iii) pre-exposure to MK-801 does not interact with conditioned taste aversion induced by lithium chloride (Experiments 4 and 5). These findings suggest that MK-801 induces a low-intensity aversion, although the underlying mechanisms of this aversion may differ from those of a conditioned aversion produced by lithium chloride.

Topics: Animals; Behavior, Animal; Conditioning, Psychological; Discrimination Learning; Dizocilpine Maleate; Dose-Response Relationship, Drug; Drinking Behavior; Dysgeusia; Excitatory Amino Acid Antagonists; Lithium Chloride; Male; Random Allocation; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate; Saccharin; Severity of Illness Index; Sweetening Agents