Aguirre N, Frechilla D, García-Osta A, Lasheras B, Del Río J
Department of Pharmacology, University of Navarra, Pamplona, Spain.
J Neurochem. 1997 Mar;68(3):1099-105. doi: 10.1046/j.1471-4159.1997.68031099.x.
The present study examined the effects of repeated administration to rats of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") on 5-hydroxytryptamine1A (5-HT1A) receptor density and mRNA expression in the hippocampus, frontal cortex, and brainstem. As expected, 7 days after subacute MDMA administration (20 mg/kg i.p. twice daily for 4 consecutive days) 5-HT content was markedly reduced (-70%) in the hippocampus and the frontal cortex. 5-HT1A receptor density was increased in the frontal cortex by 23% and decreased in the hippocampus and the brainstem by 25%. These changes correlated with an enhanced or diminished 5-HT1A receptor mRNA expression in the three regions studied. To examine the influence of corticosteroids on these changes, adrenalectomized (ADX) rats received the same dosage regimen as above. Adrenalectomy by itself did not modify 5-HT content in the brain regions examined and increased 5-HT1A receptor density in the hippocampus (+20%) but produced no change in the frontal cortex and brainstem. Adrenalectomy also prevented MDMA-induced changes in receptor number in the hippocampus and brainstem but not in the frontal cortex. Dexamethasone (1 mg/kg/day i.p.) administered for 7 consecutive days reversed the effects of adrenalectomy in the hippocampus but not in the frontal cortex. In the brainstem, MDMA no longer reduced 5-HT1A receptor number in ADX rats, but a significant reduction was restored when ADX animals received the glucocorticoid treatment. The present data show that MDMA may affect 5-HT1A receptors in a regionally dependent manner, notably through a drug effect on corticosterone release, which attenuates 5-HT1A receptor gene transcription selectively in the hippocampus.
本研究检测了对大鼠重复给予3,4-亚甲基二氧甲基苯丙胺（MDMA，“摇头丸”）对海马体、额叶皮质和脑干中5-羟色胺1A（5-HT1A）受体密度及mRNA表达的影响。正如预期的那样，亚急性给予MDMA（20毫克/千克腹腔注射，每日两次，连续4天）7天后，海马体和额叶皮质中的5-羟色胺含量显著降低（-70%）。额叶皮质中的5-HT1A受体密度增加了23%，而海马体和脑干中的则降低了25%。这些变化与所研究的三个区域中5-HT1A受体mRNA表达的增强或减弱相关。为了检测皮质类固醇对这些变化的影响，对肾上腺切除（ADX）的大鼠给予与上述相同的给药方案。肾上腺切除术本身并未改变所检测脑区中的5-羟色胺含量，且增加了海马体中的5-HT1A受体密度（+20%），但在额叶皮质和脑干中未产生变化。肾上腺切除术还阻止了MDMA诱导的海马体和脑干中受体数量的变化，但在额叶皮质中未阻止。连续7天给予地塞米松（1毫克/千克/天腹腔注射）可逆转肾上腺切除术对海马体的影响，但对额叶皮质无此作用。在脑干中，MDMA不再降低ADX大鼠中的5-HT1A受体数量，但当ADX动物接受糖皮质激素治疗时，5-HT1A受体数量又恢复了显著降低。目前的数据表明，MDMA可能以区域依赖性方式影响5-HT1A受体，特别是通过对皮质酮释放的药物作用，这会选择性地减弱海马体中5-HT1A受体基因的转录。
