MDMA ("ecstasy"), methamphetamine and their combination: long-term changes in social interaction and neurochemistry in the rat.
BACKGROUND
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 largely uncharacterised.


OBJECTIVE
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 degrees 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 the striatum.


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.
Clemens
Kelly J
KJ
School of Psychology, University of Sydney, 2006 Sydney, NSW, Australia.
Van Nieuwenhuyzen
Petra S
PS
Li
Kong M
KM
Cornish
Jennifer L
JL
Hunt
Glenn E
GE
McGregor
Iain S
IS
D000818:Animals; D001007:Anxiety / Q000139:chemically induced; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000008:administration & dosage / Q000633:toxicity; D004347:Drug Interactions; D005334:Fever / Q000139:chemically induced; D006358:Hot Temperature; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000633:toxicity*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents / Q000008:administration & dosage / Q000633:toxicity; D012919:Social Behavior
D015259:Dopamine Agents; D018490:Serotonin Agents; D012701:Serotonin; D008694:Methamphetamine; D006897:Hydroxyindoleacetic Acid; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine