Follesa P, Mancuso L, Biggio F, Cagetti E, Franco M, Trapani G, Biggio G
Department of Experimental Biology, University of Cagliari, Cagliari 09100, Italy.
Neuropharmacology. 2002 Feb;42(2):191-8. doi: 10.1016/s0028-3908(01)00167-8.
The effects of long-term treatment with and subsequent withdrawal of the two hypnotic drugs zaleplon and zolpidem on the abundance of gamma-aminobutyric acid type A (GABA(A)) receptor subunit mRNAs in cultured rat cerebellar granule cells were investigated. Incubation of neurons with either drug at a concentration of 10 microM for 5 days did not significantly affect the amounts of mRNAs encoding the alpha(1), alpha(4), beta(1), beta(2), beta(3), gamma(2)L, or gamma(2)S subunits. As expected, similar treatment with the nonselective benzodiazepine diazepam resulted in a decrease in the abundance of alpha(1), beta(2), gamma(2)L, and gamma(2)S subunit mRNAs as well as an increase in that of the beta(1) subunit mRNA. Withdrawal of zaleplon or zolpidem, like that of diazepam, induced a marked increase in the amount of the alpha(4) subunit mRNA. In addition, discontinuation of treatment with either hypnotic drug resulted in a decrease in the amounts of alpha(1), beta(2), gamma(2)L, and gamma(2)S subunit mRNAs as well as an increase in that of the beta(1) subunit mRNA. These effects of zaleplon and zolpidem on GABA(A) receptor gene expression are consistent with the reduced tolerance liability of these drugs, compared with that of diazepam, as well as with their ability to induce both physical dependence and withdrawal syndrome.
研究了两种催眠药物扎来普隆和唑吡坦长期治疗及随后撤药对培养的大鼠小脑颗粒细胞中γ-氨基丁酸A型（GABA(A)）受体亚基mRNA丰度的影响。用浓度为10微摩尔的任何一种药物孵育神经元5天，对编码α(1)、α(4)、β(1)、β(2)、β(3)、γ(2)L或γ(2)S亚基的mRNA量均无显著影响。正如预期的那样，用非选择性苯二氮䓬类药物地西泮进行类似处理，导致α(1)、β(2)、γ(2)L和γ(2)S亚基mRNA丰度降低，以及β(1)亚基mRNA丰度增加。撤去扎来普隆或唑吡坦，与撤去地西泮一样，会导致α(4)亚基mRNA量显著增加。此外，停止使用任何一种催眠药物治疗都会导致α(1)、β(2)、γ(2)L和γ(2)S亚基mRNA量减少，以及β(1)亚基mRNA量增加。扎来普隆和唑吡坦对GABA(A)受体基因表达的这些影响，与这些药物与地西泮相比耐受性降低的情况一致，也与它们诱导身体依赖性和戒断综合征的能力一致。
