D2 Receptors and Sodium Ion Channel Blockades of the Basolateral Amygdala Attenuate Lithium Chloride-Induced Conditioned Taste Aversion Applying to Cancer Chemotherapy Nausea and Vomiting

Cancer patients regularly suffer from the behavioral symptoms of chemotherapy-induced nausea and vomiting. Particularly, it is involved in Pavlovian conditioning. Lithium chloride (LiCl) was used as the unconditioned stimulus (US) and contingent with the tastant, for example, a saccharin solution (i.e., the conditioned stimulus; CS), resulted in conditioned taste aversion (CTA) to the CS intake. The present study employed an animal model of LiCl-induced CTA to imitate chemotherapy-induced nausea and vomiting symptoms. Recently, the basolateral amygdala (BLA) was shown to mediate LiCl-induced CTA learning; however, which brain mechanisms of the BLA regulate CTA by LiCl remain unknown. The present study was designed to test this issue, and 4% lidocaine or D2 blocker haloperidol were microinjected into BLA between the 0.1% saccharin solution intake and 0.15M LiCl. The results showed lidocaine microinjections into the BLA could attenuate the LiCl-induced CTA. Microinjections of haloperidol blunted the CTA learning by LiCl. Altogether, BLA via the sodium chloride ion channel and D2 receptors control LiCl-induced conditioned saccharin solution intake suppression. The findings can provide some implications and contributions to cancer chemotherapy-induced nausea and vomiting side effects, and will help to develop novel strategies to prevent the side effects of cancer chemotherapy.

Automated summary

Cancer patients often experience nausea and vomiting during chemotherapy, and this study used lithium chloride to induce conditioned taste aversion as an animal model of chemotherapy-induced symptoms. The basolateral amygdala (BLA) was found to mediate the learning of conditioned taste aversion induced by lithium chloride. Lidocaine microinjections into the BLA attenuated the aversive response, while haloperidol blunted the learning. These findings suggest that the BLA, through sodium chloride ion channels and D2 receptors, regulates the suppression of conditioned saccharin solution intake induced by lithium chloride, and can contribute to identifying strategies to prevent chemotherapy side effects.