lithium-chloride and Motion-Sickness

Following one or more chemotherapy treatments, many patients report that they experience anticipatory nausea. This phase of nausea has been interpreted as a classically conditioned response where a conditional association develops between the contextual clinic cues and the nausea and/or vomiting that developed following treatment. Although rats do not vomit, they display a distinctive gaping reaction when exposed a flavored solution previously paired with a toxin. Here we report that, even in the absence of a flavored solution, rats display conditioned gaping reactions during exposure to a distinctive context previously paired with a high dose of lithium (Experiment 1 with a distinctive odor and Experiment 3 without a distinctive odor), a low dose of lithium (Experiment 2) or provocative vestibular stimulation (Experiment 2). These results suggest that the conditioned gaping reaction in rats is selectively elicited by nausea-paired contextual stimuli, as well as flavors. This rat model of anticipatory nausea may serve as a valuable preclinical tool to evaluate the effectiveness of anti-nausea treatments and the side effect of nausea produced by newly developed pharmaceutical compounds intended for other clinical treatments.

Topics: Animals; Behavior, Animal; Conditioning, Classical; Cues; Data Interpretation, Statistical; Lithium Chloride; Male; Motion Sickness; Nausea; Odorants; Physical Stimulation; Rats; Rats, Sprague-Dawley; Rotation; Taste; Vestibule, Labyrinth; Vomiting, Anticipatory

Pairing a novel taste with provocative vestibular stimulation results in conditioned taste aversions in both rats and humans. Vestibular system involvement in gustatory conditioning was examined in sham-lesioned or labyrinthectomized rats. Three conditioning trials consisted of 30 min access to asaccharin (0.1%) solution followed by 30 min of rotation (70 rpm) or sham rotation. In a taste reactivity test with saccharin, rotated sham-lesioned rats, but not labyrinthectomized rats, exhibited increased oral rejection reactions compared with control rats. When conditioned with lithium chloride, both labyrinthectomized and sham-lesioned rats displayed robust conditioned rejection reactions. The finding that normal vestibular function is necessary in obtaining rotation-induced conditioned taste aversions supports the face and construct validity of a rat model of motion sickness.

Topics: Animals; Antimanic Agents; Avoidance Learning; Conditioning, Classical; Disease Models, Animal; Lithium Chloride; Male; Motion Sickness; Motor Activity; Rats; Rats, Sprague-Dawley; Taste; Vestibule, Labyrinth

After thermal cauterization of the area postrema in rats the absence of conditioned taste aversion to sucrose paired with lithium chloride (0.15 M, 3.3 ml/kg) was used as a pharmacologic/behavioral index of area postrema damage. In a subsequent experiment the effects of area postrema lesions on three measures proposed as species-relevant measures of motion sickness were studied, using off-vertical rotation at 150 degrees/s for either 30 or 90 min. Lesions of area postrema did not alter postrotational suppression of drinking or amount of defecation during motion. The initial acquisition of conditioned taste aversion to a novel cider vinegar solution paired with motion was not affected by lesioning of the area postrema, but these taste aversions extinguished more slowly in lesioned rats than in sham-operates or intact controls. Results are discussed in terms of proposed humoral factors which may induce motion sickness and in light of recent data on the role of the area postrema in similar measures in species possessing the complete emetic reflex.

Topics: Animals; Arousal; Avoidance Learning; Brain Mapping; Chlorides; Conditioning, Classical; Dose-Response Relationship, Drug; Drinking Behavior; Kinesthesis; Lithium; Lithium Chloride; Motion Sickness; Paraventricular Hypothalamic Nucleus; Rats; Rats, Inbred Strains; Taste