期刊
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
卷 76, 期 1, 页码 141-152出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0091-3057(03)00217-X
关键词
ecstasy; memory; tryptophan; evoked potential; CANTAB
资金
- NIDA NIH HHS [DA11004, DA09111, DA13390, R01 DA013390-02, R01 DA013390-01] Funding Source: Medline
- NIMH NIH HHS [MH47680] Funding Source: Medline
Repeated treatment with ()3,4-methylenedioylymethamphetamine (MDMA) produces lasting depletions in serotonin (5-HT) markers in the brains of New and Old World monkeys. We have previously shown that macaques treated with MDMA (4 days, 10 mg/kg im, b.i.d.), exhibit an immediate, similar to50% reduction of the 5-HT metabolite 5-hydroxymdoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) and 76-93% reductions in neocortical 5-HT content postmortem, but no lasting behavioral deficits under unchallenged conditions. Those monkeys were, however, more behaviorally sensitive to challenge with the 5-HT2C agonist 1-(3-chlorophenyl)piperazine (mCPP) I year after the NMMA regimen. A rapid tryptophan-depletion protocol was employed to determine further if these MDMA-exposed monkeys are more behaviorally and electrophysiologically sensitive to perturbation of 5-HT neurotransmission. Acute intragastric administration of a tryptophan-deficient (TRYP-) mixture of amino acids resulted in significant reductions in CSF 5-HIAA in both MDMA-exposed and control monkeys. The TRYP- mixture also reduced the brainstem auditory-evoked potential (BSAEP) P4 latency in MDMA-exposed monkeys, similar to an effect observed for 13 weeks post-MDMA. Spatial working memory performance was improved by the TRYP- mixture in the control group, but not the NDMA-exposed monkeys. Other behavioral capabilities [visual recognition memory, reaction time (RT), reinforcer efficacy and fine motor control] were not significantly affected by the TRYP- mixture in either group of monkeys. Thus, underlying alterations in brain function resulting from prior exposure to MDMA, that were not observed under normal conditions, may be revealed following perturbation of 5-HT signaling. The BSAEP response and spatial working memory appear particularly sensitive to lasting functional differences associated with MDMA exposure. (C) 2003 Elsevier Inc. All rights reserved.
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