{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:56:41Z","timestamp":1790996201073,"version":"4.1.0"},"reference-count":75,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T00:00:00Z","timestamp":1738886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Waikato Medical Research Foundation Emerging Researcher","award":["2021"],"award-info":[{"award-number":["2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Autism spectrum disorder (ASD), defined by social, behavioral, and cognitive anomalies, is also associated with dysregulated appetite. ASD individuals, often described as \u201cpicky eaters\u201d, exhibit restricted dietary preferences and a pronounced avoidance of novel foods. This suggests that the perceived safety of specific tastants may be a crucial determinant of dietary acceptance in ASD. Here, we explore the hypothesis that conditioned taste aversion (CTA), a learned avoidance of foods whose intake promotes sickness, is exacerbated in ASD. Methods: We assessed the magnitude of a lithium chloride (LiCl)-induced CTA in the valproic acid (VPA) rat model of autism versus in healthy control rats. We also examined the effect of a standard 3 mEq LiCl dose on transcript and neuronal activation changes in brain circuits mediating feeding behavior and associative learning. Results: Surprisingly, we found that while 3 mEq LiCl induced CTA in healthy controls, even the 6 mEq dose was ineffective in generating aversion in VPA rats. LiCl at 3 mEq affected c-Fos immunoreactivity in the hypothalamus and amygdala in controls, whereas in VPA rats it did not produce any c-Fos changes. Gene expression analysis of feeding-related genes (AgRP, NPY, OXT) and those involved in regulating stress and anxiety (DOR and MC3R) were differentially regulated in the VPA rats. Interestingly, transcripts for COMT1, AgRP, OXT, and MC3R were downregulated in saline-treated VPA rats compared to saline-treated controls. Conclusions: We conclude that VPA rats show blunted CTA responsiveness, which is reflected by a differential impact of LiCl on circuits that promote the acquisition of CTA in healthy versus autistic individuals.<\/jats:p>","DOI":"10.3390\/genes16020203","type":"journal-article","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T04:00:28Z","timestamp":1738900828000},"page":"203","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Neuromolecular Basis of Impaired Conditioned Taste Aversion Acquisition in Valproate-Induced Rat Model of Autism Spectrum Disorder"],"prefix":"10.3390","volume":"16","author":[{"given":"Tapasya","family":"Pal","sequence":"first","affiliation":[{"name":"School of Science, University of Waikato, Hamilton 3216, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7031-6156","authenticated-orcid":false,"given":"Savannah","family":"Harvey","sequence":"additional","affiliation":[{"name":"School of Science, University of Waikato, Hamilton 3216, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4394-2586","authenticated-orcid":false,"given":"Allen S.","family":"Levine","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawel K.","family":"Olszewski","sequence":"additional","affiliation":[{"name":"School of Science, University of Waikato, Hamilton 3216, New Zealand"},{"name":"Department of Food Science and Nutrition, University of Minnesota, St. Paul, MN 55455, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anica","family":"Klockars","sequence":"additional","affiliation":[{"name":"School of Science, University of Waikato, Hamilton 3216, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.cell.2009.10.001","article-title":"Common sense about taste: From mammals to insects","volume":"139","author":"Yarmolinsky","year":"2009","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1242\/jeb.199.7.1523","article-title":"Is chemosensory input essential for the rapid rejection of toxic foods?","volume":"199","author":"Glendinning","year":"1996","journal-title":"J. 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