α1-and α2-containing GABAA receptor modulation is not necessary for benzodiazepine-induced hyperphagia
α1-and α2-containing GABAA receptor modulation is not necessary for benzodiazepine-induced hyperphagia
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DOI：
10.1016/j.appet.2009.03.006
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发表时间：
2009-06-01
期刊：
影响因子：
5.4
通讯作者：
Clifton, P. G.
中科院分区：
文献类型：
--
作者：
Morris, H. V.;Nilsson, S.;Clifton, P. G.
Benzodiazepines increase food intake, an effect attributed to their ability to enhance palatability. We investigated which GABA(A) receptor subtypes may be involved in mediating benzodiazepine-induced hyperphagia. The role of the alpha 2 subtype was investigated by observing the effects of midazolam, on the behavioural satiety sequence in mice with targeted deletion of the alpha 2 gene (alpha 2 knockout). Midazolam (0.125, 0.25 and 0.5 mg/kg) increased food intake and the amount of time spent feeding in alpha 2 knockout mice, suggesting that BZ-induced hyperphagia does not involve alpha 2-containing GABA(A) receptors. We further investigated the roles of alpha 1- and alpha 3-containing GABA(A) receptors in mediating BZ-induced hyperphagia. We treated alpha 2(H101R) mice, in which alpha 2-containing receptors are rendered benzodiazepine insensitive, with L-838417, a compound which acts as a partial agonist at alpha 2, alpha 3 and alpha 5-receptors but is inactive at alpha 1-containing receptors. L-838417 (10 and 30 mg/kg) increased food intake and the time spent feeding in both wildtype and alpha 2(H101R) mice, demonstrating that benzodiazepine-induced hyperphagia does not require alpha 1- and alpha 2-containing GABA(A) receptors. These observations, together with evidence against the involvement of alpha 5-containing GABA(A) receptors, suggest that alpha 3-containing receptors mediate BZ-induced hyperphagia in the mouse. (C) 2009 Elsevier Ltd. All rights reserved.
