{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T12:48:07Z","timestamp":1762606087424,"version":"3.40.3"},"reference-count":19,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,4,5]],"date-time":"2012-04-05T00:00:00Z","timestamp":1333584000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2013,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We used conscious tethered Sprague\u2010Dawley rats to evaluate the cardiovascular effects of four sigma\u20101 (\u03c3<jats:sub>1<\/jats:sub>) agonists and five antagonists, given alone or in combination. All drugs were administered as a single intraperitoneal dose. The agonists were given at doses reported as efficacious in rodent cognition models, while the antagonists were administered at doses neutralizing agonist effects<jats:italic>in vivo<\/jats:italic>. Systolic blood pressure (SBP) and heart rate (HR) were continuously recorded for 20\u2003min before and 60\u2003min postadministration. Immediately after injection, a sudden, transitory increase in HR and SBP was noted in all animals, because of the stress induced by handling. For both parameters, a peak value (\u0394HR<jats:sub>max<\/jats:sub>and \u0394SBP<jats:sub>max<\/jats:sub>) and an area under the curve of changes from baseline over the period 5\u201320\u2003min postinjection (\u0394HR_AUC<jats:sub>5\u201320\u2003min<\/jats:sub>and \u0394SBP_AUC<jats:sub>5\u201320\u2003min<\/jats:sub>) were calculated. Three of the four \u03c3<jats:sub>1<\/jats:sub>agonists (SKF\u201010,047, dehydroepiandrosterone (DHEAS), Compound 14) significantly reduced \u0394HR_AUC<jats:sub>5\u201320\u2003min<\/jats:sub>value without changing \u0394HR<jats:sub>max<\/jats:sub>, while the fourth one, SA\u20104503, had no significant effect. None of the antagonists (haloperidol, rimcazole, NE\u2010100, and BD1047) reduced, and even one (progesterone) enhanced the stress\u2010induced effects on HR. No changes in SBP were noted with any compound. When the antagonist NE\u2010100 was administered just before SKF\u201010,047, it completely reversed the inhibitory effects of the \u03c3<jats:sub>1<\/jats:sub>agonist on HR increase. In conclusion, we demonstrated for the first time the involvement of \u03c3<jats:sub>1<\/jats:sub>receptors in the regulation of handling\u2010induced tachycardia in the conscious rat. Although additional investigations are needed to fully understand this role, it might offer new therapeutic perspectives to \u03c3<jats:sub>1<\/jats:sub>ligands in the cardiovascular sphere.<\/jats:p>","DOI":"10.1111\/j.1472-8206.2012.01042.x","type":"journal-article","created":{"date-parts":[[2012,4,5]],"date-time":"2012-04-05T07:12:40Z","timestamp":1333609960000},"page":"354-363","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Inhibitory effects of sigma\u20101 ligands on handling\u2010induced tachycardia in conscious tethered rats"],"prefix":"10.1111","volume":"27","author":[{"given":"Annie","family":"Delaunois","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierrette","family":"De Ron","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Detrait","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Guyaux","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,4,5]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1472-8206.2002.00063.x"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00431.2008"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.084152"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2004.028308"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00464.2007"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1039\/c1md00010a"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2008.10.010"},{"key":"e_1_2_6_9_2","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1016\/S0022-3565(25)38880-4","article-title":"Sigma receptor ligands modulate contractility, Ca++ influx and beating rate in cultured cardiac myocytes","volume":"269","author":"Ela C.","year":"1994","journal-title":"J. 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