GLUTAMATE AND COCAINE CONDITIONED LOCOMOTION

谷氨酸和可卡因条件运动

• 批准号: 6515425
• 负责人: GREGORY HOTSENPILLER
• 金额: $ 6万
• 依托单位: ROSALIND FRANKLIN UNIV OF MEDICINE & SCI
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6515425
• 关键词: behavioral /social science research tag; biological models; chordate locomotion; cocaine; conditioning; craving; drug abuse; experimental brain lesion; glutamates; laboratory rat; lidocaine; microdialysis; neuroanatomy; neuropharmacology; neurotransmitter transport; substance abuse related behavior

The initial treatment of drug addiction in a hospital setting may proceed smoothly. However, upon return to the patient's environment. intense craving often occurs and leads to relapse. Both human and animal studies have revealed that such cravings result from the association of environmental stimuli with the state of psychoactive change in a Pavlovian manner. These conditioned stimuli are powerful enough to elicit dramatic increases in craving and activation of certain brain regions in human addicts as well as behavioral changes in animals formerly treated with drugs of abuse. To study conditioned responses that may elicit craving, we will use conditioned locomotion in rats. This refers to the ability of a stimulus alone to elicit locomotor activity after it is paired repeatedly with cocaine. A discrete cue (flashing light) will be used to enable precise investigation of the control this stimulus exerts over neurochemical changes. The hypothesis to be tested is that the expression of conditioned locomotion requires increased glutamate transmission in neural circuits involving the prefrontal cortex, basolateral amygdala and nucleus accumbens. Preliminary experiments demonstrated the acquisition of conditioned locomotion to the flashing light as well as robust conditioned responses 9 days after the last pairing with cocaine. Aim l will further characterize the time course and resistance to extinction of cocaine conditioned locomotion. Aim 2 will examine the anatomical regions necessary for expression of conditioned locomotion. We had planned to use Fos as a marker for neuronal activation but found that it was not induced by conditioning with the discrete flashing light cue. Thus, regions historically found to be relevant for conditioned drug responses will be examined through lesions and lidocaine inactivation. Using the information gained from Aim 2, Aim 3 will use microdialysis to measure glutamate levels in these regions during presentation of the conditioned cue. Determining the site and pharmacological nature of the conditioned change would provide information to guide treatment attempts to block expression of such responses and thus prevent relapse.

医院环境中药物成瘾的初始治疗可能会顺利进行。但是，返回患者的环境后。强烈的渴望经常发生并导致复发。人类和动物的研究都表明，这种渴望是由于环境刺激与精神活性的状态以帕夫洛维亚的方式引起的。 这些条件的刺激足以引起人类成瘾者某些大脑地区的渴望和激活以及以前用滥用药物治疗的动物的行为改变的渴望和激活。 为了研究可能引起渴望的条件反应，我们将在大鼠中使用条件运动。这是指单独刺激与可卡因反复配对后引起运动活性的能力。 离散的提示（闪光灯）将用于对控制对控制的精确研究，这种刺激对神经化学变化产生了施加的作用。要测试的假设是，条件运动的表达需要增加涉及前额叶皮层，基底外侧杏仁核和振隔核的神经回路中的谷氨酸传播。初步实验表明，在最后一次与可卡因配对后9天，将有条件的运动恢复到闪光灯以及稳健的条件反应。 AIM L将进一步表征时间过程和抵抗可卡因调节运动的灭绝。 AIM 2将检查表达条件运动所必需的解剖区域。我们原本计划将FOS用作神经元激活的标记，但发现它不是通过与离散的闪光灯提示进行调节来诱导的。因此，历史上发现与条件药物反应有关的区域将通过病变和利多卡因失活进行检查。使用从AIM 2获得的信息，AIM 3将使用微透析来测量条件提示介绍期间这些区域中的谷氨酸水平。确定条件变化的部位和药理学性质将提供信息，以指导治疗尝试阻止这种反应的表达，从而防止复发。