{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T12:24:27Z","timestamp":1781094267989,"version":"3.54.1"},"reference-count":44,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,7,19]],"date-time":"2012-07-19T00:00:00Z","timestamp":1342656000000},"content-version":"vor","delay-in-days":6228,"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":[[1995,7]]},"abstract":"<jats:p><jats:list list-type=\"explicit-label\"><jats:list-item><jats:p>The acute inhibitory effect of selective 5\u2010hydroxytryptamine (serotonin) reuptake inhibitors (SSRIs) on 5\u2010HT neuronal activity may offset their ability to increase synaptic 5\u2010HT in the forebrain. 2Here, we determined the effects of the SSRI, paroxetine, and a novel selective 5\u2010HT<jats:sub>1A<\/jats:sub>receptor antagonist, WAY 100635, on 5\u2010HT cell firing in the dorsal raphe nucleus (DRN), and on extracellular 5\u2010HT in both the DRN and the frontal cortex (FCx). Extracellular electrophysiological recording and brain microdialysis were used in parallel experiments, in anaesthetized rats.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Paroxetine dose\u2010dependently inhibited the firing of 5\u2010HT neurones in the DRN, with a maximally effective dose of approximately 0.8 mg kg<jats:sup>\u22121<\/jats:sup>, i.v. WAY 100635 (0.1 mg kg<jats:sup>\u22121<\/jats:sup>, i.v.) both reversed the inhibitory effect of paroxetine and, when used as a pretreatment, caused a pronounced shift to the right of the paroxetine dose\u2010response curve.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>Paroxetine (0.8 mg kg<jats:sup>\u22121<\/jats:sup>, i.v.), doubled extracellular 5\u2010HT in the DRN, but did not alter extracellular 5\u2010HT in the FCx. A higher dose of paroxetine (2.4 mg kg<jats:sup>\u22121<\/jats:sup>, i.v.) did increase extracellular 5\u2010HT in the FCx, but to a lesser extent than in the DRN. Whereas 0.8 mg kg<jats:sup>\u22121<\/jats:sup>, i.v. paroxetine alone had no effect on extracellular 5\u2010HT in the FCx, in rats pretreated with WAY 100635 (0.1 mg kg<jats:sup>\u22121<\/jats:sup>), paroxetine (0.8 mg kg<jats:sup>\u22121<\/jats:sup>, i.v.) markedly increased extracellular 5\u2010HT in the FCx.<\/jats:p><\/jats:list-item><jats:list-item><jats:p>In conclusion, pretreatment with the selective 5\u2010HT<jats:sub>1A<\/jats:sub>receptor antagonist, WAY 100635, blocked the inhibitory effect of paroxetine on 5\u2010HT neuronal activity in the DRN and, at the same time, markedly enhanced the effect of paroxetine on extracellular 5\u2010HT in the FCx. These results may be relevant to recent clinical observations that 5\u2010HT<jats:sub>1A<\/jats:sub>receptor antagonists in combination with SSRIs have a rapid onset of antidepressant effect.<\/jats:p><\/jats:list-item><\/jats:list><\/jats:p>","DOI":"10.1111\/j.1476-5381.1995.tb15919.x","type":"journal-article","created":{"date-parts":[[2012,7,19]],"date-time":"2012-07-19T21:45:03Z","timestamp":1342734303000},"page":"1064-1070","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":265,"title":["Interaction between a selective 5\u2010HT<sub>1A<\/sub>receptor antagonist and an SSRI in vivo: effects on 5\u2010HT cell firing and extracellular 5\u2010HT"],"prefix":"10.1111","volume":"115","author":[{"given":"S.E.","family":"Gartside","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Umbers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Haj\u00f3s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Sharp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,7,19]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00251121"},{"key":"e_1_2_1_3_1","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1523\/JNEUROSCI.02-12-01786.1982","article-title":"Intracellular identification of central noradrenergic and serotonergic neurons by a new double labeling procedure","volume":"2","author":"AGHAJANIAN G.K.","year":"1982","journal-title":"J. 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