{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T01:42:29Z","timestamp":1780969349944,"version":"3.54.1"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T00:00:00Z","timestamp":1691971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Racemic ketamine consists of two enantiomers, namely (R)-ketamine and (S)-ketamine, with distinguishable pharmacological properties. Both enantiomers have been reported to show rapid antidepressant effects in rodents. Currently, the (S)-enantiomer has been approved for the treatment of major depression, whereas (R)-ketamine failed to show antidepressant effect in recent clinical studies. Major depressive disorder is frequently characterized by disinhibition of rapid eye movement (REM) sleep and disruption of non-REM (NREM) sleep. Racemic ketamine and most conventional antidepressants affect these parameters. However, it remains largely unknown which enantiomer is responsible for these effects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Here, we compared acute effects of the two ketamine enantiomers (15 mg\/kg i.p.) on different sleep-wake stages in freely moving, EEG-equipped rats. We also evaluated the antidepressant-like activity of the enantiomers in a chronic restraint stress model of depression.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>(S)-ketamine but not (R)-ketamine increased REM sleep latency and decreased REM sleep time at 2 and 3 hours, and increased electroencephalogram delta power during NREM sleep. In addition, only (S)-ketamine increased wakefulness and decreased NREM sleep in the first 2 hours. In the forced swimming test, only (S)-ketamine decreased the immobility time of chronically stressed rats.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Effects of the two ketamine enantiomers on rat sleep-wake architecture and behavior are markedly different when administered in the same dose. (S)-ketamine remarkably affects the sleep-wake cycle and very likely sleep-related neuroplasticity, which may be relevant for its antidepressant efficacy. Our results regarding (R)-ketamine\u2019s lack of effect on vigilance and behavior are in line with recent clinical studies.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ijnp\/pyad050","type":"journal-article","created":{"date-parts":[[2023,8,9]],"date-time":"2023-08-09T20:57:02Z","timestamp":1691614622000},"page":"618-626","source":"Crossref","is-referenced-by-count":28,"title":["(S)-Ketamine but Not (R)-Ketamine Shows Acute Effects on Depression-Like Behavior and Sleep-Wake Architecture in Rats"],"prefix":"10.1093","volume":"26","author":[{"given":"Szabolcs","family":"Koncz","sequence":"first","affiliation":[{"name":"Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University , Budapest , Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"No\u00e9mi","family":"Papp","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics, Faculty of Pharmacy, Semmelweis University , Budapest , 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