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In humans, interoceptive information is hierarchically processed in the insular cortex (IC), being integrated first in the posterior IC (PIC) and then processed in the anterior IC (AIC) to generate subjective states. However, it has not been established whether this is the case in other species nor whether utilization of interoceptive states to guide behavior is also specifically associated with functional engagement of the AIC, as suggested by this hierarchical model. We investigated in male Sprague Dawley rats whether the use of pharmacologically induced internal states to guide instrumental behavior in a discrimination task functionally engages the AIC as opposed to the mere experience of such states. Rats trained to use the interoceptive state produced by the centrally acting GABA<jats:sub>A<\/jats:sub> receptor antagonist pentylenetetrazol (PTZ) or the peripherally acting \u03b2-adrenoreceptor agonist isoproterenol to guide their behavior performed as well in a discrimination task as those trained to use an exteroceptive visual discriminative stimulus. While interoceptive internal states were as potent as exteroceptive cues to guide instrumental behavior, only the former were associated with an increase in mRNA levels of the cellular plasticity marker, zif268 in the PIC, as assessed using qPCR. In contrast, zif268 mRNA levels increased in the AIC only after rats had used PTZ-induced interoceptive states to guide behavior, not simply in response to PTZ administration. These results show that in rats, the utilization of interoceptive states to guide behavior is associated with functional engagement of the AIC.<\/jats:p>","DOI":"10.1523\/eneuro.0156-25.2025","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T21:06:22Z","timestamp":1752786382000},"page":"ENEURO.0156-25.2025","source":"Crossref","is-referenced-by-count":3,"title":["The Use of Internal States to Guide Behavior Is Associated with Functional Engagement of the Anterior Insula in Male Rats"],"prefix":"10.1523","volume":"12","author":[{"given":"Micka\u00ebl","family":"Puaud","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhaval D.","family":"Joshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7775-8860","authenticated-orcid":false,"given":"Alfie","family":"Wright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Ho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aude","family":"Belin-Rauscent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxime","family":"Fouyssac","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4431-6536","authenticated-orcid":false,"given":"Barry J.","family":"Everitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yvan","family":"Peterschmitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7383-372X","authenticated-orcid":false,"given":"David","family":"Belin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2025,7,17]]},"reference":[{"key":"2025081217451618000_12.8.ENEURO.0156-25.2025.1","doi-asserted-by":"crossref","unstructured":"Amsel A (1992) Frustration theory: an analysis of dispositional learning and memory . 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