Influences of the corticotropic axis and sympathetic activity on neurochemical consequences of 3,4-methylenedioxymethamphetamine (MDMA) administration in Fischer 344 rats.
The respective influences of the corticotropic axis and sympathetic activity on 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) immediate effects on body temperature and long-term neurotoxicity, as assessed by decreases in hippocampal and striatal [(3)H]5-hydroxytryptamine ([(3)H]5-HT) reuptake, [(3)H]paroxetine binding at 5-HT transporters (5-HTT), and 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels, were examined in Fischer 344 rats. On each of the two injections of MDMA (5 or 10 mg/kg s.c. once a day for 2 consecutive days) body temperature rapidly increased in a dose-dependent manner. Six days after the last injection of 10 mg/kg MDMA, [(3)H]5-HT reuptake, [(3)H]paroxetine binding and 5-HT and 5-HIAA levels were decreased in the hippocampus and, to a lower extent, in striatum. Prior adrenalectomy (1 week beforehand), which weakened the immediate hyperthermic effect of MDMA, prevented the long-term MDMA-elicited reduction in hippocampal and striatal [(3)H]paroxetine binding. Supplementation of adrenalectomised Fischer 344 rats with corticosterone almost reinstated the immediate hyperthermic effect of MDMA and restored MDMA-elicited reduction in hippocampal and striatal [(3)H]paroxetine binding. In a final set of experiments, Fischer 344 rats were pretreated (30 min before each of the two injections of 10 mg/kg MDMA) with the ganglionic blocker chlorisondamine (2.5 mg/kg). This pretreatment markedly reduced the amplitudes of the immediate hyperthermia and long-term declines in hippocampal [(3)H]5-HT reuptake and [(3)H]paroxetine binding at 5-HTT, and in hippocampal and striatal 5-HT and 5-HIAA levels. These results suggest that sympathetic activity (possibly through its control of body temperature), but not corticotropic activity, plays a key role in MDMA-elicited neurotoxicity in Fischer 344 rats.
Fernandez
Francesca
F
NeuroGénétique et Stress, INSERM U471-INRA, Institut F. Magendie, Rue Camille Saint Saëns, 33077 Bordeaux Cédex, France.
Aguerre
Sylvie
S
Mormède
Pierre
P
Chaouloff
Francis
F
D000302:Adrenal Cortex / Q000187:drug effects* / Q000502:physiology*; D000320:Adrenergic Fibers / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012701:Serotonin / Q000378:metabolism
D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine