Stone D M, Stahl D C, Hanson G R, Gibb J W
Eur J Pharmacol. 1986 Aug 22;128(1-2):41-8. doi: 10.1016/0014-2999(86)90555-8.
The effects of two amphetamine-like designer drugs, 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA), on dopaminergic and serotonergic systems in the rat brain were investigated and compared to those of methamphetamine (METH). Like METH, single or multiple 10 mg/kg doses of either drug caused marked reductions in both tryptophan hydroxylase (TPH) activity and concentrations of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid, in several serotonergic nerve terminal regions. In all regions examined, the reduction in 5-HT content corresponded to the depression of TPH activity. Unlike multiple METH administrations, which induced pronounced deficits in dopaminergic neuronal markers, repeated doses of MDA or MDMA did not alter striatal tyrosine hydroxylase (TH) activities or reduce striatal dopamine concentrations. A single dose of MDA or MDMA significantly elevated striatal dopamine content; however, after repeated drug administrations dopamine concentrations were comparable to control values. At this time, striatal levels of homovanillic acid were significantly elevated suggesting that both drugs influence dopamine turnover. The effects of MDA or MDMA administration in the rat brain are reminiscent of those elicited by p-chloroamphetamine, a presumed serotonergic neurotoxin.
研究了两种苯丙胺类设计药物3,4-亚甲基二氧基苯丙胺（MDA）和3,4-亚甲基二氧基甲基苯丙胺（MDMA）对大鼠脑内多巴胺能和5-羟色胺能系统的影响，并与甲基苯丙胺（METH）的影响进行了比较。与METH一样，单剂量或多剂量10mg/kg的这两种药物都会使几个5-羟色胺能神经终末区域的色氨酸羟化酶（TPH）活性以及5-羟色胺（5-HT）和5-羟吲哚乙酸的浓度显著降低。在所有检测区域，5-HT含量的降低与TPH活性的降低相对应。与多次给予METH会导致多巴胺能神经元标志物明显缺乏不同，重复给予MDA或MDMA不会改变纹状体酪氨酸羟化酶（TH）的活性，也不会降低纹状体多巴胺浓度。单剂量的MDA或MDMA会显著提高纹状体多巴胺含量；然而，在重复给药后，多巴胺浓度与对照值相当。此时，纹状体内高香草酸水平显著升高，表明这两种药物都会影响多巴胺的代谢周转。在大鼠脑内给予MDA或MDMA的效果让人联想到由对氯苯丙胺（一种假定的5-羟色胺能神经毒素）所引发的效果。
