Moret C, Briley M
Centre de Recherche Pierre Fabre, Castres, France.
Eur J Pharmacol. 1990 May 16;180(2-3):351-6. doi: 10.1016/0014-2999(90)90320-6.
Release of [3H]serotonin elicited by electrical stimulation from rat hypothalamus and its modulation through autoreceptors has been studied after chronic administration of two antidepressants, citalopram, specific inhibitor of serotonin uptake, and milnacipran (previously called midalcipran, F 2207) which blocks the uptake of serotonin and noradrenaline to the same extent. The amount of [3H]serotonin released by electrical stimulation was enhanced and the inhibitory effect of the agonist, LSD (lysergic acid diethylamide), reduced in rats treated with citalopram at 10 and 50 mg/kg per day for 21 days. These effects existed at both doses but were accentuated at the higher dose. Thus a chronic treatment with citalopram provokes a down-regulation of the serotonergic autoreceptor, allowing an increase of serotonin neurotransmission. After 21 days treatment with milnacipran, at 50 mg/kg per day, none of the parameters studied were modified. These data suggest that down-regulation of the serotonin autoreceptor is not a universally applicable hypothesis to explain the action of all antidepressants acting on the uptake of serotonin.
在长期给予两种抗抑郁药后，研究了大鼠下丘脑电刺激引发的[3H]5-羟色胺释放及其通过自身受体的调节。这两种抗抑郁药分别是5-羟色胺摄取特异性抑制剂西酞普兰，以及能同等程度阻断5-羟色胺和去甲肾上腺素摄取的米那普明（以前称为米达普明，F 2207）。在用10和50mg/kg/天的西酞普兰治疗21天的大鼠中，电刺激释放的[3H]5-羟色胺量增加，激动剂麦角酸二乙酰胺（LSD）的抑制作用降低。这两种剂量下均存在这些效应，但高剂量时更为明显。因此，长期使用西酞普兰会引发5-羟色胺能自身受体的下调，从而使5-羟色胺神经传递增加。在用50mg/kg/天的米那普明治疗21天后，所研究的参数均未改变。这些数据表明，5-羟色胺自身受体的下调并非一个普遍适用的假说来解释所有作用于5-羟色胺摄取的抗抑郁药的作用。
