{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:11:35Z","timestamp":1790903495963,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2009,2,2]],"date-time":"2009-02-02T00:00:00Z","timestamp":1233532800000},"content-version":"vor","delay-in-days":1981,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2003,9]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The nature of the cardiorespiratory effects mediated by cannabinoids in the hindbrain is poorly understood. In the present study we investigated whether cannabinoid receptor activation in the rostral ventrolateral medulla oblongata (RVLM) affects cardiovascular and\/or respiratory function.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Initially, we looked for evidence of CB<jats:sub>1<\/jats:sub> receptor gene expression in rostral and caudal sections of the rat ventrolateral medulla (VLM) using reverse transcription\u2013polymerase chain reaction. Second, the potent cannabinoid receptor agonists WIN55,212\u20102 (0.05, 0.5 or 5 pmol per 50 nl) and HU\u2010210 (0.5 pmol per 50 nl) or the CB<jats:sub>1<\/jats:sub> receptor antagonist\/inverse agonist AM281 (1 pmol per 100 nl) were microinjected into the RVLM of urethane\u2010anaesthetised, immobilised and mechanically ventilated male Sprague\u2013Dawley rats (<jats:italic>n<\/jats:italic>=22). Changes in splanchnic nerve activity (sSNA), phrenic nerve activity (PNA), mean arterial pressure (MAP) and heart rate (HR) in response to cannabinoid administration were recorded.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The CB<jats:sub>1<\/jats:sub> receptor gene was expressed throughout the VLM. Unilateral microinjection of WIN55,212\u20102 into the RVLM evoked short\u2010latency, dose\u2010dependent increases in sSNA (0.5 pmol; 175\u00b18%, <jats:italic>n<\/jats:italic>=5) and MAP (0.5 pmol; 26\u00b13%, <jats:italic>n<\/jats:italic>=8) and abolished PNA (0.5 pmol; duration of apnoea: 5.4\u00b10.4 s, <jats:italic>n<\/jats:italic>=8), with little change in HR (<jats:italic>P<\/jats:italic>&lt;0.005). HU\u2010210, structurally related to \u0394<jats:sup>9<\/jats:sup>\u2010tetrahydrocannabinol (THC), evoked similar effects when microinjected into the RVLM (<jats:italic>n<\/jats:italic>=4). Surprisingly, prior microinjection of AM281 produced agonist\u2010like effects, as well as significantly attenuated the response to subsequent injection of WIN55,212\u20102 (0.5 pmol, <jats:italic>n<\/jats:italic>=4).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The present study reveals CB<jats:sub>1<\/jats:sub> receptor gene expression in the rat VLM and demonstrates sympathoexcitation, hypertension and respiratory inhibition in response to RVLM\u2010administered cannabinoids. These findings suggest a novel link between CB<jats:sub>1<\/jats:sub> receptors in this region of the hindbrain and the central cardiorespiratory effects of cannabinoids. The extent to which these central effects contribute to the cardiovascular and respiratory outcomes of cannabis use remains to be investigated.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2003) <jats:bold>140<\/jats:bold>, 384\u2013394. doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0705422\">10.1038\/sj.bjp.0705422<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0705422","type":"journal-article","created":{"date-parts":[[2003,9,18]],"date-time":"2003-09-18T19:58:43Z","timestamp":1063915123000},"page":"384-394","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Cannabinoid receptor activation in the rostral ventrolateral medulla oblongata evokes cardiorespiratory effects in anaesthetised rats"],"prefix":"10.1111","volume":"140","author":[{"given":"James R","family":"Padley","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M","family":"Pilowsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann K","family":"Goodchild","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,2,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt1975183287"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt1979254440"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1152\/physrev.1995.75.1.1","article-title":"Central control of breathing in mammals: neuronal circuitry, membrane properties, and neurotransmitters","volume":"75","author":"BIANCHI A.L.","year":"1995","journal-title":"Physiol. 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