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Influences of the corticotropic axis and sympathetic activity on neurochemical consequences of 3,4‐methylenedioxymethamphetamine (MDMA) administration in Fischer 344 rats
Author(s) -
Fernandez Francesca,
Aguerre Sylvie,
Mormède Pierre,
Chaouloff Francis
Publication year - 2002
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.2002.02110.x
Subject(s) - mdma , neurochemical , endocrinology , serotonin , paroxetine , chemistry , medicine , ecstasy , hippocampal formation , neurotoxicity , reuptake , hippocampus , serotonin reuptake inhibitor , reuptake inhibitor , pharmacology , psychology , toxicity , antidepressant , receptor , psychiatry
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.