Activation of mu-opioid receptors in the ventral pallidum decreases the negative hedonic evaluation of a conditioned aversive taste in rats

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Conditioned taste aversion (CTA) causes a shift in the hedonic evaluation of a conditioned stimulus (CS) from positive to negative, and reduces the CS intake. Mu-opioid receptors (MORs) in the ventral pallidum (VP) are known to be involved in the hedonic evaluation of positive rewarding stimuli; however, their involvement in evaluation of a negative aversive stimulus is still unclear. To explore the neural mechanisms of the negative hedonic evaluation of the CS in CTA, we examined the effects of the activation of VP MORs on the behavioral responses of rats to a CS. Rats implanted with guide cannulae into the bilateral VP received a pairing of 5 mM saccharin solution as a CS with an intraperitoneal injection of 0.15 M lithium chloride as an unconditioned stimulus. On the test day, after microinjections of MOR agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) into the VP, we observed the behavioral responses to the intraorally infused CS solution. The DAMGO injections caused a larger number of ingestive taste reactivity responses to the CS solution. We also measured the consumption of the CS solution in a separate group of rats, using a single-bottle test. The DAMGO injected rats drank a higher volume of the CS solution than the saline injected rats. These results indicate that the activation of MORs in the VP results in the attenuation of aversion to the CS solution, thereby inducing the larger CS intake. Therefore, it is likely that VP MORs are involved in not only positive but also negative hedonic evaluation.

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