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Its pharmacological effects have not yet been adequately investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We examined a range of behavioural effects induced by acute administration of MXE (0.5\u20135\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>; i.p.) in rats and whether it causes rapid neuroadaptive molecular changes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>MXE (0.5\u20135\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>) affected motor activity in a dose\u2010 and time\u2010dependent manner, inducing hypermotility and hypomotility at low and high doses respectively. At low and intermediate doses (0.5 and 1\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>), MXE induced anxious and\/or obsessive\u2013compulsive traits (marble burying test), did not significantly increase sociability (social interaction test) or induce spatial anxiety (elevated plus maze test). At a high dose (5\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>), MXE induced transient analgesia (tail\u2010flick and hot\u2010plate test), decreased social interaction time (social interaction test) and reduced immobility time while increasing swimming activity (forced swim test), suggesting an antidepressant effect. Acute MXE administration did not affect self\u2010grooming behaviour at any dose tested. Immunohistochemical analysis showed that behaviourally active doses of MXE (1 and 5\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>) increased phosphorylation of ribosomal protein S6 in the medial prefrontal cortex and hippocampus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>MXE differentially affected motor activity, behaviour and emotional states in rats, depending on the dose tested. As reported for ketamine, phosphorylation of the ribosomal protein S6 was increased in MXE\u2010treated animals, thus providing a \u2018molecular snapshot\u2019 of rapid neuroadaptive molecular changes induced by behaviourally active doses of MXE.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13952","type":"journal-article","created":{"date-parts":[[2017,7,18]],"date-time":"2017-07-18T12:43:11Z","timestamp":1500381791000},"page":"3333-3345","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Methoxetamine affects brain processing involved in emotional response in rats"],"prefix":"10.1111","volume":"174","author":[{"given":"M T","family":"Zanda","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology University of Cagliari  Cagliari 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