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A taste associated with emetic drugs produces conditioned disgust reactions in rats (predominantly gaping), unlike nonemetic drugs that can still produce conditioned taste avoidance but not conditioned disgust. That difference suggests nausea is a prerequisite for learning disgust reactions to tastes. Depletion of forebrain serotonin (5-HT) by 5,7-dihydroxytryptamine (5,7-DHT) lesions of the dorsal raphe nucleus and median raphe nucleus prevents LiCl-induced conditioned disgust reactions (Limebeer et al., 2004). Here we demonstrate that partial depletion of 5-HT in the insular cortex (IC) prevents LiCl-induced conditioned disgust reactions. Furthermore, a double dissociation occurred in the partial regulation of disgust and taste avoidance by selective 5-HT(3) receptor antagonism/agonism in the posterior (granular) region of the IC and the anterior (dorsal agranular) region of the IC, respectively. Intracranial administration of the 5-HT(3) receptor antagonist, ondansetron (OND), to the posterior IC impaired the establishment of LiCl-induced conditioned gaping reactions, but not LiCl-induced conditioned taste avoidance (CTA). Likewise, posterior IC administration of the 5-HT(3) receptor agonist m-chlorophenylbiguanide (mCPBG) enhanced the establishment of LiCl-induced conditioned gaping and produced conditioned gaping on its own (which was prevented by intracranially administered OND), with no effect on CTA. On the other hand, anterior IC administration of OND partially reduced the establishment of LiCl-induced CTA, and mCPBG produced a weak CTA, both without effect on gaping. These results suggest that activation of 5-HT(3) receptors in the posterior IC is important for the production of nausea-induced conditioned disgust reactions, while activation of 5-HT(3) receptors in the anterior IC are involved in the production of CTA.

the journal of neuroscience/the journal of neuroscience

Double Dissociation between Regulation of Conditioned Disgust and Taste Avoidance by Serotonin Availability at the 5-HT<sub>3</sub>Receptor in the Posterior and Anterior Insular Cortex

Double Dissociation between Regulation of Conditioned Disgust and Taste Avoidance by Serotonin Availability at the 5-HT3Receptor in the Posterior and Anterior Insular Cortex

Double Dissociation between Regulation of Conditioned Disgust and Taste Avoidance by Serotonin Availability at the 5-HT₃Receptor in the Posterior and Anterior Insular Cortex