{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T04:36:04Z","timestamp":1791174964881,"version":"4.1.0"},"reference-count":63,"publisher":"National Academy of Sciences","issue":"12","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,3,19]]},"abstract":"<jats:p>\n                    Complex interactions between periphery and the brain regulate food intake in mammals. Cannabinoid type-1 (CB\n                    <jats:sub>1<\/jats:sub>\n                    ) receptor antagonists are potent hypophagic agents, but the sites where this acute action is exerted and the underlying mechanisms are not fully elucidated. To dissect the mechanisms underlying the hypophagic effect of CB\n                    <jats:sub>1<\/jats:sub>\n                    receptor blockade, we combined the acute injection of the CB\n                    <jats:sub>1<\/jats:sub>\n                    receptor antagonist rimonabant with the use of conditional\n                    <jats:italic>CB<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>1<\/jats:italic>\n                    <\/jats:sub>\n                    -knockout mice, as well as with pharmacological modulation of different central and peripheral circuits. Fasting\/refeeding experiments revealed that CB\n                    <jats:sub>1<\/jats:sub>\n                    receptor signaling in many specific brain neurons is dispensable for the acute hypophagic effects of rimonabant. CB\n                    <jats:sub>1<\/jats:sub>\n                    receptor antagonist-induced hypophagia was fully abolished by peripheral blockade of \u03b2-adrenergic transmission, suggesting that this effect is mediated by increased activity of the sympathetic nervous system. Consistently, we found that rimonabant increases gastrointestinal metabolism via increased peripheral \u03b2-adrenergic receptor signaling in peripheral organs, including the gastrointestinal tract. Blockade of both visceral afferents and glutamatergic transmission in the nucleus tractus solitarii abolished rimonabant-induced hypophagia. Importantly, these mechanisms were specifically triggered by lipid-deprivation, revealing a nutrient-specific component acutely regulated by CB\n                    <jats:sub>1<\/jats:sub>\n                    receptor blockade. Finally, peripheral blockade of sympathetic neurotransmission also blunted central effects of CB\n                    <jats:sub>1<\/jats:sub>\n                    receptor blockade, such as fear responses and anxiety-like behaviors. These data demonstrate that, independently of their site of origin, important effects of CB\n                    <jats:sub>1<\/jats:sub>\n                    receptor blockade are expressed via activation of peripheral sympathetic activity. Thus, CB\n                    <jats:sub>1<\/jats:sub>\n                    receptors modulate bidirectional circuits between the periphery and the brain to regulate feeding and other behaviors.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1218573110","type":"journal-article","created":{"date-parts":[[2013,3,5]],"date-time":"2013-03-05T06:32:33Z","timestamp":1362465153000},"page":"4786-4791","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":124,"title":["Activation of the sympathetic nervous system mediates hypophagic and anxiety-like effects of CB\n                    <sub>1<\/sub>\n                    receptor blockade"],"prefix":"10.1073","volume":"110","author":[{"given":"Luigi","family":"Bellocchio","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology I and Centro de Investigaci\u00f3n Biom\u00e9dica en Red sobre Enfermedades Neurodegenerativas, School of Biology, Complutense University-Instituto Universitario de Investigaci\u00f3n Neuroqu\u00edmica, 28040 Madrid, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Soria-G\u00f3mez","sequence":"additional","affiliation":[{"name":"Neurocentre Magendie, Physiophatologie de la Plasticit\u00e9 Neuronale, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, U862, F-33000 Bordeaux, France;"},{"name":"Neurocentre Magendie, Physiopathologie de la Plasticit\u00e9 Neuronale, U862, University of Bordeaux, F-33000 Bordeaux, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmelo","family":"Quarta","sequence":"additional","affiliation":[{"name":"Endocrinology Unit and Center for Applied Biomedical Research, Department of Medical and Surgical Sciences, S. 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