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Persistent sensitisation to the locomotor activating effects of MDMA following MDMA self-administration in rats
Susan Schenk1, Sarah Bradbury1
1Victoria University of Wellington, School of Psychology, P.O. Box 600, Wellington, New Zealand.
Abstract:
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 165mg/kg MDMA during daily 2h 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 14days following the last MDMA self-administration session and 14days following the last vehicle self-administration session. Following a 30min habituation period, rats received an injection of MDMA (10.0mg/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.
Insights
MDMA self-administration in rats led to persistent hyperactivity, indicating a sensitized response in dopamine pathways. This suggests long-term changes in brain function following repeated drug exposure.
Area of Science:
- Neuroscience
- Psychopharmacology
- Behavioral Science
Background:
- MDMA (3,4-methylenedioxymethamphetamine) exposure can lead to tolerance or sensitization depending on the regimen.
- Previous research indicates that repeated, intermittent exposure to MDMA can result in sensitized responses.
Purpose of the Study:
- To investigate the long-term effects of MDMA self-administration on MDMA-induced hyperactivity.
- To determine if voluntary MDMA intake leads to persistent changes in behavior and dopamine system activity.
Main Methods:
- Rats self-administered MDMA (165mg/kg total) or vehicle in daily sessions.
- Behavioral measures of hyperactivity (locomotion, rearing) were assessed after 5 or 14 days of abstinence.
- MDMA (10.0mg/kg, IP) was administered post-abstinence to measure hyperactivity.
Main Results:
- MDMA self-administration resulted in increased forward locomotion and rearing after both 5 and 14 days of abstinence.
- These behavioral changes suggest a persistent sensitization of dopamine substrates.
Conclusions:
- Self-administration of MDMA induces long-lasting behavioral hyperactivity in rats.
- These findings support the hypothesis of persistent dopamine system sensitization following repeated MDMA exposure.