Acute concomitant effects of MDMA binge dosing on extracellular 5-HT, locomotion and body temperature and the long-term effect on novel object discrimination in rats.
BACKGROUND
3,4-methylenedioxymethamphetamine (MDMA, ecstasy) produces an acute release of 5-HT in the brain, together with increased locomotion and hyperthermia.


OBJECTIVE
This study examined whether the acute functional changes of locomotor activity and body temperature are related to enhanced 5-HT release induced by MDMA.


METHODS
We concomitantly measured changes in extraneuronal 5-HT by in vivo brain microdialysis and used radiotelemetry to measure locomotion and body temperature to establish whether any positive correlations occur between these three parameters. 'Binge-type' repeated administration of low doses of MDMA (3 and 6 mg/kg given at 2-h intervals three times) were given to provide drug exposure similar to that experienced by recreational drug users.


RESULTS
MDMA induced acute hyperactivity, changes in core body temperature (both hypothermia and hyperthermia) and elevation of hippocampal 5-HT overflow, all of which were dependent on the dose of MDMA administered. The change in locomotor activity and the magnitude of the hyperthermia appeared to be unrelated both to each other and to the magnitude of MDMA-induced 5-HT release. The study also found evidence of long-term disruption of novel object discrimination 2 weeks following "binge-type" repeated MDMA administration.


CONCLUSIONS
MDMA-induced 5-HT release in the brain was not responsible for either the hyperthermia or increased locomotor activity that occurred. Since neither dose schedule of MDMA induced a neurotoxic loss of brain 5-HT 2 weeks after its administration, the impairment of recognition memory found in novel object discrimination probably results from other long-term changes yet to be established.
Rodsiri
Ratchanee
R
School of Biomedical Sciences, Medical School, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
Spicer
Clare
C
Green
A Richard
AR
Marsden
Charles A
CA
Fone
Kevin C F
KC
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005334:Fever / Q000139:chemically induced; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D017551:Microdialysis; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000008:administration & dosage / Q000494:pharmacology*; D013686:Telemetry / Q000379:methods
D018490:Serotonin Agents; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine