The ketamine-like compound methoxetamine substitutes for ketamine in the self-administration paradigm and enhances mesolimbic dopaminergic transmission.
Psychopharmacology June 1, 2016 Anna Mutti, Sonia Aroni, Paola Fadda et al.
Methoxetamine (MXE), a novel ketamine-like drug increasingly linked to emergency cases, was tested in male rats trained to self-administer ketamine. Low doses of MXE (0.125 and 0.25 mg/kg) substituted for ketamine self-administration, while the highest dose (0.5 mg/kg) did not. MXE dose-dependently increased the firing rate and burst firing of dopamine neurons in the ventral tegmental area projecting to the nucleus accumbens shell. It also raised dopamine levels in that brain region, with a 0.5 mg/kg dose having a faster onset (40 minutes) than 0.25 mg/kg (100 minutes). These findings indicate MXE has reinforcing and addiction-related properties.