KAPPA OPIOID AGONISTS AND COCAINE SENSITIZATION
KAPPA 阿片受体激动剂和可卡因致敏作用
基本信息
- 批准号:2013442
- 负责人:
- 金额:$ 18.39万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1997
- 资助国家:美国
- 起止时间:1997-02-20 至 1999-11-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION: (Applicant's Abstract)
The proposed studies aim to characterize the site and mechanism of action of
kappa-opioid receptor agonists in preventing the sensitization or
"reverse-tolerance" which develops to the rewarding effects of cocaine
following its repeated administration. Our objectives are to determine
whether: 1) activation of kappa-opioid receptors located in regions
comprising the mesocorticolimbic dopamine (DA) system, is sufficient to
prevent the sensitization which develops to the rewarding effects of
cocaine; 2) the modulatory effects of systemically and intracerebrally
administered kappa-agonists upon sensitization are correlated with a
suppression of cocaine-induced increases in extracellular DA levels within
the nucleus accumbens (NAC), a projection site of mesocorticolimbic neurons
and 3) inactivation of kappa-opioid receptors exacerbates the development of
the sensitization process. The conditioned place preference and intravenous
self-administration paradigms, will be used to map the site of action of
kappa-agonists in modulating the development of sensitization and to examine
whether microinjection of a kappa-opioid receptor antagonists exacerbate the
development of sensitization. The technique of microdialysis will be used
to monitor extracellular DA levels within the NAC in response to the
administration of cocaine and kappa-opioid receptor ligands. We hypothesize
that exogenously applied kappa-opioid agonists prevent sensitization to the
rewarding effects of cocaine by activating opioid receptors located within
the NAC and thereby suppressing cocaine-induced increases in extracellular
DA levels within this specific brain region. These studies will provide
important information regarding the site of action of kappa-opioid agonists
in modulating adaptive behavioral responses which occur in response to
repeated cocaine administration and may contribute to the development of an
effective pharmacological treatment for cocaine addiction.
描述:(申请人摘要)
拟议的研究旨在表征的网站和作用机制,
κ-阿片受体激动剂在预防致敏或
“反向耐受”,发展到可卡因的奖励作用
经过多次管理。 我们的目标是确定
是否:1)激活位于区域中的κ-阿片受体
包括中皮质边缘多巴胺(DA)系统,足以
防止敏感性发展到奖励效果,
可卡因; 2)全身和脑内的调节作用
在致敏时给予的κ-激动剂与
抑制可卡因诱导的细胞外DA水平的增加,
中脑皮质边缘神经元的投射部位--中脑核
和3)κ-阿片受体的失活加剧了
敏化过程。 条件性位置偏爱和静脉注射
自我管理范例,将被用来映射的作用网站,
κ-激动剂在调节致敏作用发展中的作用,
微量注射κ-阿片受体拮抗剂是否会加剧
提高敏感性。 将采用微透析技术
为了监测NAC内的细胞外DA水平,
给予可卡因和κ-阿片样物质受体配体。 我们假设
外源性应用κ-阿片样物质激动剂可防止对
可卡因通过激活阿片受体的奖励作用,
NAC,从而抑制可卡因诱导的细胞外
多巴胺水平在这个特定的大脑区域。 这些研究将提供
关于κ-阿片激动剂作用部位的重要信息
在调节适应性行为反应中,
重复使用可卡因,可能有助于发展
可卡因成瘾的有效药物治疗。
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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SUSAN PICKETT其他文献
SUSAN PICKETT的其他文献
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{{ truncateString('SUSAN PICKETT', 18)}}的其他基金
JOURNEY OF HOPE FAMILY EDUCATION COURSE OUTCOMES
希望之旅家庭教育课程成果
- 批准号:
6032177 - 财政年份:2000
- 资助金额:
$ 18.39万 - 项目类别:
JOURNEY OF HOPE FAMILY EDUCATION COURSE OUTCOMES
希望之旅家庭教育课程成果
- 批准号:
6392687 - 财政年份:2000
- 资助金额:
$ 18.39万 - 项目类别:
JOURNEY OF HOPE FAMILY EDUCATION COURSE OUTCOMES
希望之旅家庭教育课程成果
- 批准号:
6528609 - 财政年份:2000
- 资助金额:
$ 18.39万 - 项目类别:
JOURNEY OF HOPE FAMILY EDUCATION COURSE OUTCOMES
希望之旅家庭教育课程成果
- 批准号:
6653051 - 财政年份:2000
- 资助金额:
$ 18.39万 - 项目类别:
KAPPA OPIOID AGONISTS AND COCAINE SENSITIZATION
KAPPA 阿片受体激动剂和可卡因致敏作用
- 批准号:
2608209 - 财政年份:1997
- 资助金额:
$ 18.39万 - 项目类别:
MECHANISMS OF ENVIROMENTAL INFLUENCES ON COCAINE REWARD
环境影响可卡因奖励的机制
- 批准号:
3461144 - 财政年份:1988
- 资助金额:
$ 18.39万 - 项目类别: