The ketamine analogue methoxetamine generalizes to ketamine discriminative stimulus in rats.
Cristiano Chiamulera, Federica Armani, Anna Mutti, Liana Fattore
Behavioural Pharmacology April 1, 2016 DOI: 10.1097/fbp.0000000000000221 (opens in new tab) via PubMed
Summary
AI-generated from the abstractMethoxetamine (MXE), a chemical analogue of ketamine, fully substitutes for ketamine in a drug discrimination test in rats, indicating shared subjective and potentially addictive properties. Rats trained to distinguish ketamine from a placebo generalized the ketamine stimulus to MXE and to the NMDA channel blocker MK-801, but only partially to lysergic acid and methamphetamine. The highest dose of lysergic acid produced 77.7% generalization. These results suggest that evaluating novel ketamine-like drugs should consider not only chemical and molecular similarities but also overlapping psychopharmacological effects.
Study at a glance
| Characteristics | Animal model, drug discrimination study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Methoxetamine MK-801 lysergic acid methamphetamine |
| Dose | 0.0625, 0.125, 0.25, 0.5, or 1.0 mg/kg for MXE; 0.005-0.1 mg/kg for MK-801; 0.025-0.30 mg/kg for lysergic acid; 0.15-0.60 mg/kg for methamphetamine |
| Key finding | Methoxetamine and MK-801 fully generalized to the ketamine discriminative stimulus in rats, while lysergic acid and methamphetamine only partially substituted. |
Abstract
Methoxetamine (MXE) is a chemical analogue of ketamine. Originally proposed as a ketamine-like fast-acting antidepressant, owing to similar N-methyl-D-aspartate blocker properties, it is now scheduled for reports of hallucinations and psychosis similar to ketamine and lysergic acid. As little is known about the addictive properties of MXE, the aim of this study was to investigate the similarity between discriminative stimuli of MXE and ketamine, as well as to provide data and protocols that could be used in the future for the characterization of novel ketamine-like drugs. The paradigm used was a two-lever operant conditioning paradigm in which rats were trained to discriminate ketamine (7.5 mg/kg/ml, intraperitoneal) from vehicle. Generalization tests were performed with MXE (0.0625, 0.125, 0.25, 0.5, or 1.0). We also tested the N-methyl-D-aspartate channel blocker MK-801 (0.005-0.1), lysergic acid (0.025-0.30), a serotonergic drug that had similar hallucinogenic effects as ketamine and methamphetamine (0.15-0.60) a drug with no generalization with ketamine, injected intraperitoneally presession (mg/kg). MXE and MK-801 fully generalized to ketamine. Lysergic acid and methamphetamine partially substituted for the ketamine stimulus, although the highest lysergic acid dose showed a 77.7% generalization. The present findings suggest that investigation of 'ketamine-like compounds' should explore not only substances with chemical analogy and common molecular mechanisms with ketamine, but also with similar psychopharmacological effects.