The distribution of gamma-hydroxybutyrate-induced Fos expression in rat brain: comparison with baclofen.

作者:

PSV NieuwenhuijzenIS McgregorGE Hunt

展开

摘要:

γ-Hydroxybutyrate (GHB) is a euphoric, prosocial and sleep inducing drug that binds with high affinity to its own GHB receptor site and also more weakly to GABAB receptors. GHB is efficacious in the treatment of narcolepsy and alcoholism, but heavy use can lead to dependence and withdrawal. Many effects of GHB (sedation, hypothermia, catalepsy) are mimicked by GABAB receptor agonists (e.g. baclofen). However other effects (euphoric and prosocial effects and a therapeutic effect in narcolepsy) are not. The present study used Fos immunohistochemistry to assess the neural activation produced in rat brain by medium to high doses of GHB (250, 500 and 1000 mg/kg) and a high dose of baclofen (10 mg/kg) that produced similar sedation to 500 mg/kg GHB. Results showed many common regions of activation with these two drugs including the supraoptic, paraventricular, median preoptic and ventral premammillary nuclei of the hypothalamus, the central nucleus of the amygdala, Edinger-Westphal nucleus, lateral parabrachial nucleus, locus coeruleus, and nucleus of the solitary tract. GHB (500 mg/kg), but not baclofen (10 mg/kg), induced significant Fos expression in the median raphe nucleus and lateral habenula, while a higher dose of GHB (1000 mg/kg) induced additional Fos expression in the islands of Calleja, dentate gyrus (polymorphic layer) and arcuate nucleus, and in various regions implicated in rapid and non-rapid eye movement sleep (laterodorsal tegmental nucleus, tuberomammillary nucleus and the ventrolateral and anterodorsal preoptic nuclei). Surprisingly, Fos immunoreactivity was not observed with either GHB or baclofen in reward-relevant regions such as the nucleus accumbens, striatum and ventral tegmental area. Overall these results indicate a distinctive signature of brain activation with GHB that may be only partly due to GABAB receptor effects. This confirms a unique neuropharmacological profile for GHB and indicates key neural substrates that may underlie its characteristic influence on sleep, body temperature, sociability and endocrine function.

展开

DOI:

10.1016/j.neuroscience.2008.10.011

被引量:

124

年份:

2009

通过文献互助平台发起求助,成功后即可免费获取论文全文。

我们已与文献出版商建立了直接购买合作。

你可以通过身份认证进行实名认证,认证成功后本次下载的费用将由您所在的图书馆支付

您可以直接购买此文献,1~5分钟即可下载全文,部分资源由于网络原因可能需要更长时间,请您耐心等待哦~

身份认证 全文购买

相似文献

参考文献

引证文献

来源期刊

Neuroscience
23 January 2009

引用走势

2010
被引量:23

辅助模式

0

引用

文献可以批量引用啦~
欢迎点我试用!

引用