{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T01:29:13Z","timestamp":1777858153350,"version":"3.51.4"},"reference-count":46,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2002,3,1]],"date-time":"2002-03-01T00:00:00Z","timestamp":1014940800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Psychopharmacol"],"published-print":{"date-parts":[[2002,3]]},"abstract":"<jats:p>\n                    Clinical augmentation strategies have shown that some improvement in antidepressant efficacy can be achieved by combining the \u03b2-adrenergic\/serotonin (5-HT)1A\/1B receptor antagonist (\u00b1)pindolol with a selective serotonin reuptake inhibitor (SSRI). This has lead to the hypothesis that a combination of a 5-HT\n                    <jats:sub>1A<\/jats:sub>\n                    receptor antagonist with an SSRI will lead to a faster onset of antidepressant action. Although there is a significant accumulation of acute preclinical data supporting this rationale, until recently, there have been no investigations examining the chronic effects of combining an SSRI with a 5-HT\n                    <jats:sub>1A<\/jats:sub>\n                    receptor antagonist. Here, we determined the chronic effects of fluoxetine (10 mg\/kg o.d.), administered in combination with the selective 5-HT\n                    <jats:sub>1A<\/jats:sub>\n                    receptor antagonist WAY-100635 (1 mg\/kg b.i.d.), on serotonergic neurotransmission in the frontal cortex using in-vivo microdialysis. Following chronic administration of fluoxetine \u00b1 WAY-100635, functional changes in serotonergic neurotransmission, as well as 5-HT\n                    <jats:sub>1A<\/jats:sub>\n                    autoreceptors, were assessed by administering fluoxetine or (\u00b1) 8-hydroxy-2-(di-n-propylamino)tetralin [(\u00b1) 8-OH-DPAT] 24 h after the last chronic dose. Chronic administration of WAY-100635 alone produced no detectable change in the functional status of the 5-HT\n                    <jats:sub>1A<\/jats:sub>\n                    receptor. However, fluoxetine alone produced a time-dependent adaptation in serotonergic transmission such that fluoxetine (acutely administered on day 15) was able to produce a two fold increase in extracellular 5-HT levels but the decrease in response to 8-OH-DPAT was completely attenuated. These data indicate that the fluoxetine-induced adaptation was mediated by desensitization of the 5-HT\n                    <jats:sub>1A<\/jats:sub>\n                    receptor. WAY-100635 given chronically in combination with fluoxetine blocked the SSRI-induced desensitization of the 5-HT\n                    <jats:sub>1A<\/jats:sub>\n                    receptor. Furthermore, chronic treatment with this combination produced no tolerance in terms of its ability to acutely increase forebrain 5-HT levels. These data suggest that augmentation of an SSRI by combined pharmacotherapy with a 5-HT\n                    <jats:sub>1A<\/jats:sub>\n                    antagonist would be effective upon prolonged exposure.\n                  <\/jats:p>","DOI":"10.1177\/026988110201600205","type":"journal-article","created":{"date-parts":[[2009,4,1]],"date-time":"2009-04-01T19:04:54Z","timestamp":1238612694000},"page":"145-152","source":"Crossref","is-referenced-by-count":56,"title":["Effect of chronic fluoxetine and WAY-100635 treatment on serotonergic neurotransmission in the frontal cortex"],"prefix":"10.1177","volume":"16","author":[{"given":"L. A.","family":"Dawson","sequence":"first","affiliation":[{"name":"Neuroscience Research, Wyeth Ayerst, Princeton, NJ, USA; Neuropharmacology, Psychiatry CEDD, Glaxo Smith Kline, New Frontiers Science Park (North), Harlow, Essex CM19 5AW, UK;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. Q.","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. L.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L. 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