Rationale: 3,4-Methylenedioxymethamphetamine (MDMA) and methamphetamine
(METH) are illicit drugs that are increasingly used in combination.
The acute and long-term effects of MDMA/METH combinations are
Objectives: The current study investigated the behavioural, thermal
and neurotoxic effects of MDMA and METH when given alone or in
combined low doses.
Methods: Male rats received four injections, one every 2 h, of
vehicle, MDMA (2.5 or 5 mg/ kg per injection), METH (2.5 or 5
mg/kg per injection) or combined MDMA/METH (1.25+1.25 mg/kg per
injection or 2+2 mg/kg per injection). Drugs were given at an
ambient temperature of 28°C to simulate hot nightclub conditions.
Body temperature, locomotor activity and head-weaving were assessed
during acute drug administration while social interaction, anxiety-related
behavior on the emergence test and neurochemical parameters were
assessed 4-7 weeks later.
Results: All treatments acutely increased locomotor activity,
while pronounced head-weaving was seen with both MDMA/METH treatments
and the higher dose METH treatment. Acute hyperthermia was greatest
with the higher dose MDMA/ METH treatment and was also seen with
MDMA but not METH treatment. Several weeks after drug administration,
both MDMA/METH groups, both METH groups and the higher dose MDMA
group showed decreased social interaction relative to controls,
while both MDMA/ METH groups and the lower dose MDMA group showed
increased anxiety-like behaviour on the emergence test. MDMA treatment
caused 5-HT and 5-HIAA depletion in several brain regions, while
METH treatment reduced dopamine in the prefrontal cortex. Combined
MDMA/ METH treatment caused 5-HT and 5-HIAA depletion in several
brain regions and a unique depletion of dopamine and DOPAC in
Conclusions: These results suggest that MDMA and METH in combination
may have greater adverse acute effects (head-weaving, body temperature)
and long-term effects (decreased social interaction, increased
emergence anxiety, dopamine depletion) than equivalent doses of
either drug alone.