Ondansetron blocks LiCl-induced conditioned place avoidance but not conditioned taste/flavor avoidance in rats

The ability of an experimental agent to support conditioned taste/flavor avoidance (CT/FA) in rats often is interpreted as sufficient evidence that the agent produced a state of malaise or nausea. Paradoxically, however, CT/FA also is induced by certain drugs that support conditioned preferences in rats, suggesting that CT/FA is insufficient to reveal a negative hedonic state. The present study tested the hypothesis that the anti-nausea drug ondansetron (OND) would block the ability of nauseogenic lithium chloride (LiCl) to support conditioned place avoidance (CPA), without attenuating LiCl-induced CT/FA. After pre-treatment with either OND or vehicle, rats were conditioned with i.p. injection of 0.15 M LiCl containing 2% saccharin (LiCl + sac) on conditioning day 1, and with 0.15 M NaCl alone on conditioning day 2. Rats were confined to a distinct chamber of a CPA apparatus after each conditioning injection. In other rats, OND or vehicle pre-treatment was followed by NaCl + sac on conditioning day 1, and LiCl alone on day 2. Subsequent testing revealed that OND blocked the ability of LiCl to support CPA. Conversely, in the same rats, OND did not alter the ability of LiCl to condition avoidance of 0.2% sac solution during a 60 min bottle test. In a separate experiment, a sensitive 2-bottle choice test was used to confirm that OND pre-treatment does not reduce the ability of LiCl to support CT/FA. These results support the view that CPA is an additional useful tool to reveal the experience of malaise and nausea in rats, whereas CT/FA demonstrated in bottle intake tests is insufficient for this purpose.