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Ghrelin, an orexigenic hormone, activates agouti related peptide (AgRP) neurons in the arcuate nucleus to promote food intake. Here, we investigated the hypothesis that increased sensitivity to ghrelin during pregnancy and lactation may contribute to elevated maternal food intake. Acute food intake was measured after a single dose of ghrelin or vehicle across reproductive states including virgin, pregnant (Day 8 and Day 15), lactating (Day 10) mice and dams 2\u2009weeks after weaning. In vivo GCaMP fibre photometry of the AgRP neuron population was used to measure AgRP neuronal response to ghrelin. Unlike virgin mice, pregnant mice did not show an acute increase in food intake after ghrelin injection, while ghrelin\u2010treated lactating mice showed a greater feeding response than virgin mice. After weaning, dams showed a similar increase in food intake to that seen in virgin mice. In contrast to the loss of feeding response to ghrelin, the expected increase in growth hormone (GH) in response to ghrelin was observed in both pregnancy and lactation. Across all of the reproductive states, a significant increase in AgRP neuron activity was observed in response to exogenous ghrelin administration, although the magnitude was slightly reduced in late pregnancy. Furthermore, the ghrelin\u2010induced increase in c\u2010Fos expression in AgRP neurons was similar in all reproductive states, indicating that AgRP neurons remained responsive to ghrelin despite the absence of a food\u2010intake response to ghrelin during pregnancy. Interestingly, the expected drop in AgRP neuron activity in response to the presentation of food was absent during late pregnancy and lactation. The absence of a food consumption\u2010mediated inhibition of AgRP neuron activity suggests that an attenuated response of the AgRP neurons to feedback signals associated with eating may contribute to increases in meal duration during pregnancy and lactation. Overall, these results indicate that ghrelin resistance develops during pregnancy, suggesting that ghrelin does not contribute to elevated food intake during pregnancy. In lactation, however, enhanced ghrelin sensitivity may contribute to elevated maternal food intake. These results also indicate that adaptations to ghrelin sensitivity in pregnancy and lactation are transient as 2\u2009weeks after weaning our results are similar to the virgin state.<\/jats:p>","DOI":"10.1111\/jne.70202","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T05:59:33Z","timestamp":1781071173000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Altered responses to ghrelin and food cues in\n                    <scp>AgRP<\/scp>\n                    neurons during pregnancy and lactation"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4678-0601","authenticated-orcid":false,"given":"C. L.","family":"Murrell","sequence":"first","affiliation":[{"name":"Department of Psychiatry Washington University in St. Louis  St Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. R.","family":"Perkinson","sequence":"additional","affiliation":[{"name":"Centre for Neuroendocrinology and Department of Physiology School of Biomedical Sciences, University of Otago  Dunedin New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9097-7944","authenticated-orcid":false,"given":"Z. B.","family":"Andrews","sequence":"additional","affiliation":[{"name":"Monash Biomedicine Discovery Institute and Department of Physiology Monash University  Clayton Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5606-2559","authenticated-orcid":false,"given":"D. R.","family":"Grattan","sequence":"additional","affiliation":[{"name":"Centre for Neuroendocrinology and Department of Anatomy, School of Biomedical Sciences University of Otago  Dunedin New Zealand"},{"name":"Maurice Wilkins Centre for Molecular Biodiscovery  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. R.","family":"Ladyman","sequence":"additional","affiliation":[{"name":"Centre for Neuroendocrinology and Department of Anatomy, School of Biomedical Sciences University of Otago  Dunedin New Zealand"},{"name":"Maurice Wilkins Centre for Molecular Biodiscovery  Auckland New 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