Diazepam-induced changes on sleep and the EEG spectrum in mice:: role of the α3-GABAA receptor subtype
Diazepam-induced changes on sleep and the EEG spectrum in mice:: role of the α3-GABAA receptor subtype
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DOI：
10.1046/j.1460-9568.2003.02651.x
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发表时间：
2003-05-01
影响因子：
3.4
通讯作者：
Tobler, I
中科院分区：
文献类型：
--
作者：
Kopp, C;Rudolph, U;Tobler, I
苯二氮卓类药物通过调节结合位点增强GABA（A）受体的GABA能神经传递，从而减少非REM睡眠中的EEG慢波活动。然而，苯二氮卓类药物对睡眠和睡眠EEG影响的潜在作用机制仍不清楚。睡眠中的慢波由皮质丘脑系统产生，并由丘脑网状核的抑制性GABA能神经元同步。该区域仅含有含α 3的GABA（A）受体。我们通过研究α 3-GABA（A）受体对地西泮不敏感的点突变小鼠[α 3（H126 R）]，研究了这些受体在地西泮对睡眠EEG影响的介导中的作用。在alpha 3（H126 R）和野生型对照（n=13-17/基因型）中，在轻度发作时腹膜内注射3 mg/kg地西泮或溶媒后记录睡眠12小时。主要影响是在非REM睡眠中慢波活动（EEG功率密度在0.75-4.00 Hz）的显着减少，以及在非REM睡眠和清醒中15.00 Hz以上频率的伴随增加。地西泮的作用在基因型之间没有显著差异。尽管含有α 3的GABA（A）受体在丘脑网状核中唯一表达，但这些受体似乎对地西泮对睡眠EEG的调节作用并不重要。
Benzodiazepines reduce EEG slow-wave activity in non-REM sleep by potentiating GABAergic neurotransmission at GABA(A) receptors via a modulatory binding site. However, the mechanisms of action underlying the effects of benzodiazepines on sleep and the sleep EEG are still unknown. Slow waves during sleep are generated by the corticothalamic system and synchronized by the inhibitory GABAergic neurons of the reticular thalamic nucleus. This region contains exclusively alpha3-containing GABA(A) receptors. We investigated the role of these receptors in the mediation of diazepam effects on the sleep EEG by studying point-mutated mice in which the alpha3-GABA(A) receptor is diazepam-insensitive [alpha3(H126R)]. Sleep was recorded for 12 h after i.p. injection of 3 mg/kg diazepam or vehicle at light onset in alpha3(H126R) and wild-type controls (n=13-17 per genotype). The main effect was a marked reduction of slow-wave activity (EEG power density in 0.75-4.00 Hz) in non-REM sleep and a concomitant increase in frequencies above 15.00 Hz in non-REM sleep and waking in both genotypes. Neither effect of diazepam differed significantly between the genotypes. Despite the exclusive expression of alpha3-containing GABA(A) receptors in the reticular thalamic nucleus, these receptors do not seem to be critical for the mediation of the effects of diazepam on the sleep EEG.