α1- and α2-containing GABA A receptor modulation is not necessary for benzodiazepine-induced hyperphagia
| Autor: | Claire I. Dixon, H.V. Morris, Simon R. O. Nilsson, Peter G. Clifton, D.N. Stephens |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty medicine.drug_class Midazolam Hyperphagia Partial agonist gamma-Aminobutyric acid Hypnotic Benzodiazepines Mice Random Allocation Internal medicine medicine Animals GABA-A Receptor Agonists GABA Modulators Receptor General Psychology Mice Knockout Analysis of Variance Benzodiazepine Diazepam Nutrition and Dietetics Dose-Response Relationship Drug GABAA receptor digestive oral and skin physiology Triazoles Receptors GABA-A Fluorobenzenes Endocrinology Knockout mouse Female Energy Intake Psychology medicine.drug |
| Zdroj: | Appetite. 52:675-683 |
| ISSN: | 0195-6663 |
| DOI: | 10.1016/j.appet.2009.03.006 |
| Popis: | 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 alpha2 subtype was investigated by observing the effects of midazolam, on the behavioural satiety sequence in mice with targeted deletion of the alpha2 gene (alpha2 knockout). Midazolam (0.125, 0.25 and 0.5mg/kg) increased food intake and the amount of time spent feeding in alpha2 knockout mice, suggesting that BZ-induced hyperphagia does not involve alpha2-containing GABA(A) receptors. We further investigated the roles of alpha1- and alpha3-containing GABA(A) receptors in mediating BZ-induced hyperphagia. We treated alpha2(H101R) mice, in which alpha2-containing receptors are rendered benzodiazepine insensitive, with L-838417, a compound which acts as a partial agonist at alpha2-, alpha3- and alpha5-receptors but is inactive at alpha1-containing receptors. L-838417 (10 and 30 mg/kg) increased food intake and the time spent feeding in both wildtype and alpha2(H101R) mice, demonstrating that benzodiazepine-induced hyperphagia does not require alpha1- and alpha2-containing GABA(A) receptors. These observations, together with evidence against the involvement of alpha5-containing GABA(A) receptors, suggest that alpha3-containing receptors mediate BZ-induced hyperphagia in the mouse. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect