Chronic alnespirone-induced desensitization of somatodendritic 5-HT1A autoreceptors in the rat dorsal raphe nucleus

被引:14
作者
Le Poul, E
Laaris, N
Doucet, E
Fattaccini, CM
Mocaér, E
Hamon, M
Lanfumey, L
机构
[1] Fac Med Pitie Salpetriere, INSERM U288, F-75634 Paris 13, France
[2] Inst Rech Int Servier, F-92415 Courbevoie, France
关键词
alnespirone; 5-HT receptor; 5-HT1A; autoreceptor; dorsal raphe nucleus; nerve impulse flow; autoradiography;
D O I
10.1016/S0014-2999(98)00886-3
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The effects of long-term (7, 14, or 21 days) administration of the 5-HT1A receptor agonist alnespirone [5 mg/(kg day), i.p.] on the binding characteristics of 5-HT1A,5-HT2A and 5-HT3 receptors, and the functional status of 5-HT1A autoreceptors were assessed using biochemical and electrophysiological approaches in rats. Whatever the treatment duration, the specific binding of [H-3]8 hydroxy-2-(di-n-propylamino)tetralin ([H-3]8-OH-DPAT), [H-3]trans,4-[(3Z)3-(2-dimethylaminoethyl) oxyimino-3(2-fluorophenyl) propen-1-yl] phenol hemifumarate ([H-3]SR 46349B), and [H-3]S-zacopride to 5-HT1A, 5-HT2A and 5-HT3 receptors, respectively, were unaltered in all the brain areas examined. In contrast, in vitro electrophysiological recordings performed 24 h after the last injection of alnespirone showed that the potency of the 5-HT1A receptor agonist, 8-OH-DPAT, to depress the firing of serotoninergic neurons in the dorsal raphe nucleus, was significantly reduced after a 21-day treatment with alnespirone. However, no changes were noted after a 7-day or 14-day treatment. These data indicate that desensitization of somatodendritic 5-HT1A autoreceptors is a selective but slowly developing adaptive phenomenon in response to their chronic stimulation in rats. (C) 1999 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:165 / 173
页数:9
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