PHYSIOLOGY AND PHARMACOLOGY OF OPIOIDS IN BRAIN
脑中阿片类药物的生理学和药理学
基本信息
- 批准号:2443457
- 负责人:
- 金额:$ 12.94万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1992
- 资助国家:美国
- 起止时间:1992-07-01 至 2000-05-31
- 项目状态:已结题
- 来源:
- 关键词:biological signal transduction calcium channel cholecystokinin electrophysiology endogenous opioid gamma aminobutyrate hippocampus inhibitor /antagonist interneurons laboratory rat neural transmission neurochemistry neuropeptides nitric oxide opioid receptor periaqueductal gray matter stimulant /agonist tissue /cell culture voltage gated channel
项目摘要
Opioids are known to have important behavioral and physiological actions
that are mediated by interactions with neurons in the central nervous
system. However, while the behavioral actions of the opioids, including
analgesia and euphoria, are well-known, the functional roles these
molecules play as neuromodulators in the mammalian brain remain poorly
understood. The following experiments will evaluate the actions of
opioids, acting at pharmacologically defined mu-, delta- and kappa-opioid
receptor subtypes, as modulators of synaptic transmission in the CA1 and
dentate gyrus regions of the hippocampus, and in another brain region
known as the periaqueductal gray. The experiments described in this
proposal will utilize whole-cell patch clamp electrophysiological
techniques to examine the effects of opioids on individual neurons in rat
brain slice preparations. The first set of experiments will focus on the
mechanisms through which mu-, delta-, and kappa-opioid receptor agonists
act to decrease evoked and spontaneous synaptic transmission in the
hippocampal slice. In particular, these experiments will examine the
contributions made by distinct voltage-dependent calcium channels,
intracellular calcium stores, and nitric oxide in supporting synaptic
transmission and the modulation of this process. The second set of
experiments will determine the effects of opioid agonists directly on
subpopulations of gamma-aminobutyric acid (GABA)-containing neurons
(interneurons) in the CA1 region of the hippocampus, and the cellular
mechanisms these receptors utilize to affect these cells. These
experiments will be aided through the use of differential interference
contrast microscopy to identify these neurons in living brain slices. The
third set of experiments will determine what mechanisms account for the
ability of certain non-opioid peptides to attenuate the behavioral and
cellular actions of the opioids. Thus, we will determine the effects of
the peptides cholecystokinin (CCK) and neuropeptide FF on neurons found in
the hippocampus, and the periaqueductal gray. The investigations described
in this grant proposal should improve our understanding of the specific
receptor subtypes that the opioids act upon, the cellular mechanisms
mediating their responses, the roles opioids may play as neuromodulators
in the brain, and the mechanism of their interaction with other non-opioid
peptides. in addition, since limbic structures like the hippocampus have
been shown to participate in normal and abnormal behavioral states such as
learning, epilepsy, and emotional behavior, and the periaqueductal gray
has been shown to be important in mediating opioid analgesia, these
studies may yield new insights as to the interaction between opioids and
these phenomena.
阿片类药物已知具有重要的行为和生理作用。
它是通过与中枢神经中的神经元相互作用来调节的
系统。然而,虽然阿片类药物的行为行为,包括
止痛和快感,是众所周知的,这些功能作用
分子发挥作用,哺乳动物大脑中的神经调节器仍然很弱
明白了。下面的实验将评估
阿片类药物,作用于药理学定义的Mu-、Delta-和Kappa-阿片
受体亚型,作为CA1和CA1区突触传递的调节器
海马齿状回区域,以及在另一个大脑区域
被称为中脑导水管周围灰质。本文件中描述的实验
方案将利用全细胞膜片钳电生理
阿片类药物对大鼠单个神经元影响的检测技术
脑片准备。第一组实验将集中在
U-阿片受体激动剂、β-阿片受体激动剂和kappa-阿片受体激动剂的作用机制
减少诱发的和自发的突触传递
海马片。特别是,这些实验将检验
不同的电压依赖性钙通道的贡献,
支持突触的细胞内钙储存和一氧化氮
这一过程的传输和调制。第二套
实验将直接确定阿片激动剂对
γ-氨基丁酸(GABA)神经元亚群
(中间神经元)在海马区CA1区,以及细胞
这些受体用来影响这些细胞的机制。这些
实验将通过使用差分干涉得到帮助
对比显微镜在活体脑片中识别这些神经元。这个
第三组实验将确定是什么机制解释了
某些非阿片肽能够减弱行为和
阿片类药物的细胞活动。因此,我们将确定
胆囊素(CCK)和神经肽FF对大鼠神经元的影响
海马体和中脑导水管周围灰质。所描述的调查
在这项赠款提案中,应该提高我们对具体
阿片类药物作用的受体亚型,细胞机制
阿片类药物作为神经调节剂可能扮演的角色
以及它们与其他非阿片类药物相互作用的机制
多肽。此外,由于海马体等边缘结构
被证明参与正常和异常的行为状态,例如
学习、癫痫和情绪行为,以及中脑导水管周围灰质
已被证明在介导阿片类止痛方面很重要,这些
研究可能会对阿片和阿片之间的相互作用产生新的见解
这些现象。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Carl R. Lupica其他文献
Absence of sex differences in serotonergic control of orbitofrontal cortex neuronal activity
血清素能对眶额叶皮质神经元活动的控制中不存在性别差异
- DOI:
10.1038/s41598-025-11208-2 - 发表时间:
2025-07-17 - 期刊:
- 影响因子:3.900
- 作者:
Kailin M. Mooney;Alexander F. Hoffman;Carl R. Lupica - 通讯作者:
Carl R. Lupica
Carl R. Lupica的其他文献
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{{ truncateString('Carl R. Lupica', 18)}}的其他基金
PHYSIOLOGY AND PHARMACOLOGY OF OPIOIDS IN BRAIN
脑中阿片类药物的生理学和药理学
- 批准号:
2120217 - 财政年份:1992
- 资助金额:
$ 12.94万 - 项目类别:
PHYSIOLOGY AND PHARMACOLOGY OF OPIOIDS IN BRAIN
脑中阿片类药物的生理学和药理学
- 批准号:
2120216 - 财政年份:1992
- 资助金额:
$ 12.94万 - 项目类别:
PHYSIOLOGY AND PHARMACOLOGY OF OPIOIDS IN BRAIN
脑中阿片类药物的生理学和药理学
- 批准号:
2897879 - 财政年份:1992
- 资助金额:
$ 12.94万 - 项目类别:
Cocaine Addiction and the Role of Serotonin in Orbitofrontal Cortex Function
可卡因成瘾和血清素在眶额皮层功能中的作用
- 批准号:
8933873 - 财政年份:
- 资助金额:
$ 12.94万 - 项目类别:
Effect Of Drugs of Abuse On Synaptic Transmission In Nucleus Accumbens
滥用药物对伏核突触传递的影响
- 批准号:
8933812 - 财政年份:
- 资助金额:
$ 12.94万 - 项目类别:
Physiology of mitochondrial dysfunction in genetic models of Parkinson's disease
帕金森病遗传模型中线粒体功能障碍的生理学
- 批准号:
7733846 - 财政年份:
- 资助金额:
$ 12.94万 - 项目类别:
Physiology of mitochondrial dysfunction in genetic models of Parkinson's disease
帕金森病遗传模型中线粒体功能障碍的生理学
- 批准号:
8148545 - 财政年份:
- 资助金额:
$ 12.94万 - 项目类别:
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