Methoxetamine, a ketamine derivative, produced conditioned place preference and was self-administered by rats: Evidence of its abuse potential.
Chrislean Jun Botanas, J. B. de la Peña, I. J. D. Dela Peña, Reinholdgher Tampus, Robin Yoon, H. Kim, Yong Sup Lee, C. Jang, J. Cheong
Pharmacology, Biochemistry, and Behavior June 1, 2015 DOI: 10.1016/j.pbb.2015.03.007 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Sprague-Dawley rats |
| Interventions | Methoxetamine Ketamine |
| Dose | MXE: 2.5 and 5 mg/kg (CPP), 0.25, 0.5, 1.0 mg/kg/infusion (SA); Ketamine: 5 mg/kg (CPP), 0.5 mg/kg/infusion (SA) |
| Topics | Esketamine Ketamine |
| Key findings | MXE produced significant conditioned place preference at 2.5 and 5 mg/kg, comparable to ketamine at 5 mg/kg, and modest self-administration at 0.25, 0.5, and 1.0 mg/kg/infusion, while ketamine at 0.5 mg/kg/infusion was robustly self-administered. MXE did not alter locomotor activity, whereas ketamine decreased it. The authors suggest MXE has abuse potential and warrants regulation. |
Abstract
Methoxetamine (MXE) is an N-methyl-d-aspartate (NMDA) receptor antagonist that is chemically and pharmacologically similar to ketamine. Recently, there have been many reports regarding its use/misuse in humans which have resulted in serious or even fatal outcomes. Despite these reports, MXE is not controlled or regulated in many countries which may be partly due to the lack of scientific evidence regarding its abuse potential. Thus, in the present study we evaluated the abuse potential (rewarding and reinforcing effects) of MXE through the conditioned place preference (CPP) and self-administration (SA) tests in Sprague-Dawley rats. In addition, locomotor activity during the conditioning phase of the CPP was also analyzed. Ketamine was used as a reference drug. MXE (2.5 and 5mg/kg) induced significant CPP in rats, an effect comparable to that of ketamine (5mg/kg). Interestingly, MXE did not produce any locomotor alterations while ketamine decreased the locomotor activity of rats. In the SA test, rats showed modest self-administration of MXE (0.25, 0.5, 1.0mg/kg/infusion), while ketamine (0.5mg/kg/infusion) was robustly self-administered. These results demonstrate that MXE, similar to ketamine, has rewarding and reinforcing effects in rats. The present study strongly suggests that MXE has a potential for human abuse. In addition, the discrepant effects of MXE and ketamine on locomotor activity and rate of self-administration propose that the psychopharmacological effects of these drugs may diverge in some aspects. More importantly, this study advocates the careful monitoring and prompt regulation of MXE and its related substances.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 34
- The abuse liability of ketamine: A scoping review of preclinical and clinical studies. Journal of Psychiatric Research May 1, 2022
- On the safety of repeated ketamine infusions for the treatment of depression: Effects of sex and developmental periods Neurobiology of Stress September 21, 2018
- Use and abuse of dissociative and psychedelic drugs in adolescence Pharmacology, Biochemistry, and Behavior January 27, 2021
- Detailed pharmacological evaluation of methoxetamine (MXE), a novel psychoactive ketamine analogue—Behavioural, pharmacokinetic and metabolic studies in the Wistar rat Brain Research Bulletin May 4, 2016
- Ketamine use disorder: preclinical, clinical, and neuroimaging evidence to support proposed mechanisms of actions Intelligent Medicine March 7, 2022
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Cites 11
- Ketamine use: a review Addiction July 21, 2011
- Beyond THC: The New Generation of Cannabinoid Designer Drugs Frontiers in Behavioral Neuroscience 2011
- From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs. Drug Testing and Analysis 2014
- Phenomenon of new drugs on the Internet: the case of ketamine derivative methoxetamine Human Psychopharmacology: Clinical and Experimental March 1, 2012
- The ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor. PLoS One June 14, 2016
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