ELECTROCONVULSIVE SHOCK EFFECTS ON BRAIN RECEPTORS
ELECTROCONVULSIVE SHOCK EFFECTS ON BRAIN RECEPTORS
批准号:
3380666
负责人:
KENNETH J KELLAR
金额:
$15.06万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1986
资助国家:
美国
项目状态:
已结题
起止时间:
1986-07-01 至 1991-06-30
关键词:
alpha adrenergic receptor amphetamines antidepressants autoradiography axon beta adrenergic receptor brain mapping brain metabolism cyclic AMP electroconvulsive therapy experimental brain lesion imipramine laboratory rat mental disorder chemotherapy neurochemistry neurotransmitter receptor norepinephrine p chlorophenylalanine phenelzine phosphatidylinositols radiotracer serotonin
中文摘要
这项研究的总体目标是比较
电惊厥性休克(ECS)给药的效果
抗抑郁药物对5-羟色胺能和去甲肾上腺素能的影响
大鼠大脑中的受体。特别是,以下内容
将检验假设:1)ECS与MOST不同
抗抑郁药物治疗对5-羟色胺-2的影响
受体,以及2)ECS与大多数抗抑郁药不同
药物治疗对上调β-肾上腺素能的影响
感受器。为了检验后一种假设,我们将使用一个新的
5-羟色胺高度特异性损伤后的模型
神经元或抑制5-羟色胺合成,β-肾上腺素能
大脑中的受体显著增加。在具体的
本研究的目的是:1)确定ECS的效果
而抗抑郁药物的数量增加了
通过测定配体结合和β-肾上腺素能受体
异丙肾上腺素刺激脑内环磷酸腺苷的产生。2)至
使用定量放射自显影来识别和比较
β-肾上腺素能受体所在的特定脑区
被ECS和抗抑郁药物降低,并确定
β受体亚型受这些处理的影响。3)至
用定量放射自显影识别特定区域
以及大脑皮层中5-羟色胺-2受体的层
ECS升高,抗抑郁药降低。4)至
体外循环与抗抑郁药对5-羟色胺-2的影响比较
和α-1-肾上腺素能受体介导的肌醇磷脂
水解液。5)确定去甲肾上腺素的损害是否
轴突改变ECS或抗抑郁药物对
5-HT-2受体。
这些研究应该会提供有关影响的新信息。
ECS和抗抑郁药物在受体系统上的作用
两种神经递质最常被牵连到
抑郁症及其治疗。此信息应为
有助于对神经化学物质的最终理解
ECS和抗抑郁药物的影响以及对潜在的
电休克治疗临床效果的理论基础。
英文摘要
The overall objectives of this research are to compare the
effects of administration of electroconvulsive shock (ECS) and
antidepressant drugs on serotonergic and noradrenergic
receptors in rat brain. In particular, the following
hypotheses will be tested: 1) that ECS differs from most
antidepressant drug treatments in its effects on 5-HT-2
receptors, and 2) that ECS differs from most antidepressant
drug treatments in its effects on up-regulated beta-adrenergic
receptors. To test the latter hypothesis, we will use a new
model in which following highly specific lesions of 5-HT
neurons or inhibition of 5-HT synthesis, beta-adrenergic
receptors are markedly increased in brain. Among the specific
aims of this research are: 1) To determine the effects of ECS
and antidepressant drugs on the increased number of
beta-adrenergic receptors by measuring ligand binding and
isoproterenol-stimulated cyclic AMP production in brain. 2) To
use quantitative autoradiography to identify and compare the
specific brain regions in which beta-adrenergic receptors are
decreased by ECS and antidepressant drugs, and to identify the
beta receptor subtype affected by these treatments. 3) To
identify by quantitative autoradiography the specific regions
and layers of cerebral cortex in which 5-HT-2 receptors are
increased by ECS and decreased by antidepressant drugs. 4) To
compare the effects of ECS and antidepressant drugs on 5-HT-2
and alpha-1-adrenergic receptor-mediated phosphoinositide
hydrolysis. 5) To determine whether lesions of norepinephrine
axons alter the effects of ECS or antidepressant drugs on
5-HT-2 receptors.
These studies should provide new information about the effects
of ECS and antidepressant drugs on the receptor systems for the
two neurotransmitters that have been most often implicated in
depression and its treatment. This information should
contribute to an eventual understanding of the neurochemical
effects of ECS and antidepressant drugs and potentially to the
rationale for the clinical effects of electroconvulsive therapy.
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Electroconvulsive shocks increase the concentration of neocortical and hippocampal neuropeptide Y (NPY)-like immunoreactivity in the rat.
电休克会增加大鼠新皮质和海马神经肽 Y (NPY) 样免疫反应性的浓度。
DOI:
10.1016/0006-8993(90)90523-e
发表时间:
1990
期刊:
Brain research
影响因子:
2.9
作者:
[Wahlestedt,C, Blendy,JA, Kellar,KJ, Heilig,M, Widerlöv,E, Ekman,R]
通讯作者:
Ekman,R
Electroconvulsive shock and reserpine increase alpha 1-adrenoceptor binding sites but not norepinephrine-stimulated phosphoinositide hydrolysis in rat brain.
电休克和利血平会增加大鼠脑中α1-肾上腺素受体的结合位点,但不会增加去甲肾上腺素刺激的磷酸肌醇水解。
DOI:
10.1016/0014-2999(88)90330-5
发表时间:
1988
期刊:
European journal of pharmacology
影响因子:
5
作者:
[Blendy,JA, Stockmeier,CA, Kellar,KJ]
通讯作者:
Kellar,KJ
Electroconvulsive shock increases alpha 1b- but not alpha 1a-adrenoceptor binding sites in rat cerebral cortex.
电休克会增加大鼠大脑皮层中 α1b- 肾上腺素受体的结合位点,但不会增加 α1a- 肾上腺素受体的结合位点。
DOI:
10.1111/j.1471-4159.1991.tb06350.x
发表时间:
1991
期刊:
Journal of neurochemistry
影响因子:
4.7
作者:
[Blendy,JA, Perry,DC, Pabreza,LA, Kellar,KJ]
通讯作者:
Kellar,KJ
Electroconvulsive shock differentially increases binding to alpha-1 adrenergic receptor subtypes in discrete regions of rat brain.
电休克不同程度地增加了大鼠大脑离散区域中与 α-1 肾上腺素能受体亚型的结合。
DOI:
10.1523/jneurosci.10-08-02580.1990
发表时间:
1990
期刊:
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子:
--
作者:
[Blendy,JA, Grimm,LJ, Perry,DC, West-Johnsrud,L, Kellar,KJ]
通讯作者:
Kellar,KJ
Electroconvulsive shock but not antidepressant drugs increases alpha 1-adrenoceptor binding sites in rat brain.
电休克会增加大鼠大脑中的α1-肾上腺素受体结合位点,但抗抑郁药物不会增加。
DOI:
10.1016/0014-2999(87)90582-6
发表时间:
1987
期刊:
European journal of pharmacology
影响因子:
5
作者:
[Stockmeier,CA, McLeskey,SW, Blendy,JA, Armstrong,NR, Kellar,KJ]
通讯作者:
Kellar,KJ
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