Persistent sensitisation to the locomotor activating effects of MDMA following MDMA self-administration in rats

Effects of MDMA exposure on MDMA-produced hyperactivity are dependent on the exposure regimen; high-dose exposure produced tolerance whereas repeated, intermittent exposure produced sensitised responses. In the present study we measured the impact of MDMA self-administration on MDMA-produced hyperactivity. Rats self-administered a total of 165 mg/kg MDMA during daily 2 h sessions. Control rats self-administered vehicle solution and were matched to the MDMA self-administering rats so that they had the same number of daily exposures to handling and the chamber. Behavioural measures were collected either 5 or 14 days following the last MDMA self-administration session and 14 days following the last vehicle self-administration session. Following a 30 min habituation period, rats received an injection of MDMA (10.0 mg/kg, IP) and various measures of MDMA-produced hyperactivity were measured. Speed of forward locomotion and rearing, behaviours that are often attributed to dopaminergic mechanisms, increased following both abstinence periods. These data are consistent with a persistent sensitisation of dopamine substrates as a result of MDMA self-administration.