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Repeated weekly exposure to MDMA, methamphetamine or their combination: long-term behavioural and neurochemical
Kelly J Clemens1, Jennifer L Cornish, Glenn E Hunt
1School of Psychology, University of Sydney, NSW 2006, Australia. kclemens@psy.unsw.edu.au
Abstract:
In recent work we have documented lasting adverse neurochemical and behavioural effects in rats given short-term 'binge' dosing with methylenedioxymethamphetamine (MDMA, Ecstasy), methamphetamine (METH) or their combination. Here we investigated whether similar effects persist in rats given 16 weekly injections followed by a 10 week period of abstinence. Female rats received MDMA (8 mg/kg, i.p.), METH (8 mg/kg), or a MDMA/METH combination (4 mg/kg MDMA + 4 mg/kg METH), once a week for 16 weeks, with locomotor activity and body temperature measured on weeks 1, 8 and 16. The MDMA and MDMA/METH groups showed acute drug-induced hyperthermia on week 1 only. MDMA-treated rats demonstrated an acute hyperactivity while METH and MDMA/METH treated rats showed pronounced stereotypy. Seven weeks after drug-treatment concluded, a decrease in social interaction was observed in all chronically drug-treated rats. No group differences were evident on the emergence, object recognition or forced swim tests. Neurochemical analysis revealed modest noradrenaline and serotonin depletion in chronically treated rats that was not evident following a single equivalent administration. These results indicate that although chronic, intermittent exposure to MDMA, METH or their combination, may not lead to significant long-term monoamine depletion, lasting adverse behavioural effects may persist, especially those related to social behaviour.
Insights
Chronic intermittent exposure to methylenedioxymethamphetamine (MDMA) and methamphetamine (METH) in rats caused lasting social behavior deficits. Neurochemical depletions were modest, but behavioral changes persisted after abstinence.
Area of Science:
- Neuroscience
- Psychopharmacology
- Behavioral Science
Background:
- Previous research documented lasting neurochemical and behavioral effects from short-term binge dosing of MDMA and METH.
- The persistence of these effects after longer-term, intermittent exposure and abstinence remained unclear.
Purpose of the Study:
- To investigate if chronic, intermittent exposure to MDMA, METH, or their combination leads to lasting adverse neurochemical and behavioral effects in rats.
- To assess the persistence of these effects following a 10-week abstinence period.
Main Methods:
- Female rats received weekly injections of MDMA, METH, or a combination for 16 weeks.
- Locomotor activity, body temperature, and social interaction were measured.
- Neurochemical analyses were performed, and behavioral tests (emergence, object recognition, forced swim) were conducted.
Main Results:
- Acute hyperthermia and hyperactivity/stereotypy were observed during dosing.
- A significant decrease in social interaction was evident in all drug-treated groups after 10 weeks of abstinence.
- Modest, non-persistent noradrenaline and serotonin depletion was noted, unlike effects after single administrations.
Conclusions:
- Chronic, intermittent exposure to MDMA, METH, or their combination does not appear to cause significant long-term monoamine depletion.
- Lasting adverse behavioral effects, particularly deficits in social behavior, persist even after a prolonged abstinence period.
- These findings highlight the potential for long-term behavioral consequences of repeated stimulant drug use.
