Methoxetamine affects brain processing involved in emotional response in rats

BACKGROUND AND PURPOSEMethoxetamine (MXE) is a novel psychoactive substance that is emerging on the Intern et and induces dissociat ive effects andacute toxicity. Its pharmacological effects have not yet been adequatel y investigated.EXPERIMENTAL APPROACHWe examined a r ange of behavioura l effects induced by a cute admi nistration of MXE (0.5-5mg·kg?1; i.p.) in rats and whe ther itcauses rapid neuroadaptive molecular changes.KEY RESULTSMXE (0.5-5mg·kg?1) affected motor activity in a dose- and tim e-dependent manner, inducing h ypermoti lity and hypomotility atlow and high doses r espectively. At low and intermediate doses (0.5 and 1 mg·kg?1), MXE induced anxious an d/orobsessive-compulsive traits (marble burying test), did not significantly increase sociability (social intera ction test) or induce spatialanxiety (elevated plus maze test). At a h igh dose (5 mg·kg?1), MXE induced transient analgesia (tail-flick and hot-plate test),decreased social interaction time (social intera ction test) and re duced immobilit y time while increa sing swimming activity ( force dswim test) , suggesting an antidepressant effect. Acute MXE administration did not affect self-grooming behaviour at any dosetested. Immunohistochemical a nalysis showed that behaviourally active doses of MXE (1 and 5 mg·kg?1) in creased phosphor y-lation of ribosomal protein S6 in the medial pr efrontal cortex and hippocampus.CONCLUSIONS AND IMPLICATIONSMXE different ially affected motor activity, behaviour and emotio nal states in rats, depending on the dose t ested. A s reporte d forketamine, phosphorylation of the ribosomal protein S6 was increased in MXE-treated animals, thus providing a 'molecularsnapshot' of rapid neuroadaptive molecular changes induced by behaviour ally active doses of MXE