Influences of the corticotropic axis and sympathetic activity on neurochemical consequences of 3,4-methylenedioxymethamphetamine (MDMA) administration in Fischer 344 rats
European Journal of Neuroscience. 2002-08-01; 16(4): 607-618
DOI: 10.1046/j.1460-9568.2002.02110.x
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1. Eur J Neurosci. 2002 Aug;16(4):607-18.
Influences of the corticotropic axis and sympathetic activity on neurochemical
consequences of 3,4-methylenedioxymethamphetamine (MDMA) administration in
Fischer 344 rats.
Fernandez F(1), Aguerre S, Mormède P, Chaouloff F.
Author information:
(1)NeuroGénétique et Stress, INSERM U471-INRA, Institut F. Magendie, Rue Camille
Saint Saëns, 33077 Bordeaux Cédex, France.
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.
DOI: 10.1046/j.1460-9568.2002.02110.x
PMID: 12270036 [Indexed for MEDLINE]