Related Experiment Video
Updated: Feb 26, 2026
An Olfactory Preference Test for Measuring Olfactory Hedonic Biases in Mouse Models of Depression
Published on: July 11, 2025
Methoxetamine affects brain processing involved in emotional response in rats
M T Zanda1, P Fadda1, S Antinori1
1Department of Biomedical Sciences, Division of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy.
Background And Purpose:
Methoxetamine (MXE) is a novel psychoactive substance that is emerging on the Internet and induces dissociative effects and acute toxicity. Its pharmacological effects have not yet been adequately investigated.
Experimental Approach:
We examined a range of behavioural effects induced by acute administration of MXE (0.5-5 mg·kg-1 ; i.p.) in rats and whether it causes rapid neuroadaptive molecular changes.
Key Results:
MXE (0.5-5 mg·kg-1 ) affected motor activity in a dose- and time-dependent manner, inducing hypermotility and hypomotility at low and high doses respectively. At low and intermediate doses (0.5 and 1 mg·kg-1 ), MXE induced anxious and/or obsessive-compulsive 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 mg·kg-1 ), MXE induced transient analgesia (tail-flick and hot-plate 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-grooming behaviour at any dose tested. Immunohistochemical analysis showed that behaviourally active doses of MXE (1 and 5 mg·kg-1 ) increased phosphorylation of ribosomal protein S6 in the medial prefrontal cortex and hippocampus.
Conclusions And Implications:
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-treated animals, thus providing a 'molecular snapshot' of rapid neuroadaptive molecular changes induced by behaviourally active doses of MXE.
Insights
Methoxetamine (MXE) alters rat behavior and motor activity in a dose-dependent manner, with high doses showing antidepressant effects. This study reveals rapid neuroadaptive changes in the brain following MXE administration.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Methoxetamine (MXE) is a novel psychoactive substance with emerging online availability.
- MXE induces dissociative effects and acute toxicity, but its pharmacological profile remains under-investigated.
Purpose of the Study:
- To investigate the behavioral effects of acute MXE administration in rats.
- To determine if MXE causes rapid neuroadaptive molecular changes in the brain.
Main Methods:
- Acute intraperitoneal administration of MXE (0.5-5 mg·kg⁻¹) to rats.
- Assessment of motor activity, anxiety-like behaviors, sociability, and antidepressant-like effects.
- Immunohistochemical analysis of ribosomal protein S6 phosphorylation in the medial prefrontal cortex and hippocampus.
Main Results:
- MXE affected motor activity in a dose-dependent manner (hypermotility at low doses, hypomotility at high doses).
- Low to intermediate MXE doses induced anxiety- and obsessive-compulsive-like behaviors.
- High MXE doses demonstrated transient analgesia and antidepressant-like effects, with increased S6 phosphorylation in the prefrontal cortex and hippocampus.
Conclusions:
- MXE exerts differential effects on behavior and emotional states in rats based on dosage.
- Acute MXE administration induces rapid neuroadaptive molecular changes, evidenced by increased S6 phosphorylation, similar to ketamine.
