{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:42:08Z","timestamp":1791214928611,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,2,5]],"date-time":"2009-02-05T00:00:00Z","timestamp":1233792000000},"content-version":"vor","delay-in-days":3902,"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":[[1998,6]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Debate exists as to the nature of antidepressant\u2010induced antinociception. It is unclear whether antidepressants are inherently antinociceptive, are able to potentiate opioid antinociception or both. We have used the acetic acid induced abdominal constriction assay in mice to investigate antidepressant\u2010induced antinociception.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>All the antidepressants tested (s.c.) produced dose\u2010dependent protection against acetic acid\u2010induced abdominal constriction. Similarly, morphine and aspirin were also effective antinociceptive agents in this nociceptive assay.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Opioid antagonists, naloxone (0.5 mg kg<jats:sup>\u22121<\/jats:sup>, s.c.) and naltrindole (1 mg kg<jats:sup>\u22121<\/jats:sup>, s.c.), shifted the dose\u2010response relationships to the right for each of the antidepressant agents (dothiepin, amitriptyline, sibutramine, (+)\u2010oxaprotiline and paroxetine). In this context the naloxone dose\u2010ratios were 1.95, 3.90, 2.32, 4.50 and 2.65, with naltrindole dose\u2010ratios of 4.36, 17.00, 4.28, 11.48 and 2.65 were obtained, respectively. Naloxone also shifted the morphine dose\u2010response relationship to the right, by a factor of 2.62, whilst naltrindole had no effect upon morphine antinociception. Aspirin antinociception remained unaffected by both opioid antagonists.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The enkephalin catabolism inhibitor acetorphan, by itself, produced no activity in this test at a dose of 10 mg kg<jats:sup>\u22121<\/jats:sup> (s.c.). However, at higher doses, acetorphan produced a linear dose\u2010response relationship against acetic acid\u2010induced abdominal constriction.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>When acetorphan was administered before either the antidepressants or morphine, there was a clear potentiation of the antidepressant\u2010 or morphine\u2010induced antinociception. However, acetorphan had no effect on aspirin antinociception.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Since neither of the opioid antagonists were able to attenuate, nor was acetorphan able to potentiate, aspirin antinociception, we concluded that the mechanism of antidepressant\u2010induced antinociception is different from that of the non\u2010steroidal anti\u2010inflammatory drugs.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>These data are consistent with the view that antidepressants may induce endogenous opioid peptide release, as shown by the acetorphan study. In this context, the ability of naltrindole to displace the antidepressant dose\u2010response relationship to the right without affecting morphine antinociception, implicates the \u03b4\u2010opioid receptor and endogenous opioid peptides in antidepressant\u2010induced antinociception.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p>","DOI":"10.1038\/sj.bjp.0701882","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:30:35Z","timestamp":1106940635000},"page":"669-674","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":116,"title":["The involvement of the opioidergic system in the antinociceptive mechanism of action of antidepressant compounds"],"prefix":"10.1111","volume":"124","author":[{"given":"A M","family":"Gray","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P S J","family":"Spencer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R D E","family":"Sewell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,2,5]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(79)90073-X"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(80)90531-6"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410130209"},{"key":"e_1_2_5_5_1","first-page":"593","article-title":"Inhibitors of enkephalinase: the next generation of analgesics","volume":"11","author":"Chipkin R.E.","year":"1986","journal-title":"Drugs of the Future"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(85)90247-X"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(89)90702-4"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bdj.4805304"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.36.4.684"},{"key":"e_1_2_5_10_1","first-page":"22","article-title":"Doxepin effects on chronic pain, depression and plasma opioids","volume":"43","author":"Hameroff S.R.","year":"1982","journal-title":"J. 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