NEURAL MECHANISMS IN THE NUCLEUS ACCUMENS AND BEHAVIOR

据估计，目前有200多万种常规药物 这个国家的用户。两大类药物，精神刺激剂和 鸦片类药物构成了所使用的大多数非法物质。强迫症 这些药物的使用和滥用构成了重大的社会和医学问题 有问题。药物滥用的潜在原因是复杂的，涉及 社会、心理和生物因素的相互作用。目标是 神经生物学研究的核心是了解大脑是如何受到影响的 并被这些化合物改变。尽管许多大脑区域可能 受药物使用的影响，人们特别关注核团 伏隔，一种介于边缘系统和前脑之间的前脑结构 马达系统。过去的研究表明，伏隔核 调节两种刺激剂(可卡因和可卡因)的增强特性 安非他命)和鸦片类药物(海洛因和吗啡)。目前的提案 寻求进一步研究神经递质的相互作用和信号 伏核内的转导机制，使用一种 大鼠的行为-药理学方法。为了实现这一目标， 直接脑内注射神经递质或药物将是 与测量运动的行为范例结合使用 活动，对条件性奖励的反应，以及探索。确实有 这些实验的三个主要目标：1)调查 谷氨酸介导的皮质边缘传入伏隔核 精神刺激剂和鸦片类药物的行为影响。我们还将研究 谷氨酸在正常适应行为中的作用 伏隔核，如探索和空间学习。2)至 研究伏隔核内阿片剂与多巴胺的相互作用， 特别关注阿片类药物诱导的现象 对安非他明和可卡因交叉敏感。3)研究 在行为中特定的信号转导机制由 伏隔核，以及对这些系统的操纵可能如何改变 对精神刺激剂和鸦片类药物的行为反应。为了这些 实验中，伏隔核内微量注射细菌毒素 选择性干扰G蛋白将联合进行 关于运动活动和条件反射反应的研究 增援。这个项目的结果可能有助于进步。 两个领域的知识：1)更详细地了解 精神刺激剂和药物引起的行为和神经化学变化 鸦片类药物；2)进一步了解特定神经系统的作用 在伏隔核内的行为。

It is estimated that there are presently over 2,000,000 regular drug users in this country. Two major classes of drugs, psychostimulants and opiates, comprise the majority of illicit substances used. Compulsive use and abuse of these drugs constitutes a major social and medical problem. The causes underlying drug abuse are complex, involving interactions of social, psychological and biological factors. The goal of neurobiological research is to understand how the brain is affected and changed by these compounds. Although many brain regions may be affected by drug use, particular focus has been given to the nucleus accumbens, a forebrain structure interposed between the limbic system and the motor system. Past research has shown that the nucleus accumbens mediates the reinforcing properties of both stimulants (cocaine and amphetamine) and opiates (heroin and morphine). The current proposal seeks to further examine neurotransmitter interactions and signal transduction mechanisms within the nucleus accumbens, using a behavioral-pharmacological approach in the rat. To accomplish this goal, direct brain microinjection of neurotransmitters or drugs will be employed in conjunction with behavioral paradigms that measure motor activity, responding for conditioned reward, and exploration. There are three major objectives of these experiments: 1) To investigate the role of glutamate-mediated corticolimbic input to the nucleus accumbens in the behavioral effects of psychostimulants and opiates. We will also study the role of glutamate in normal adaptive behavior subserved by the nucleus accumbens, such as exploration and spatial learning. 2) To investigate opiate-dopamine interactions in the nucleus accumbens, focusing particularly on the phenomenon of opiate-induced cross-sensitization to amphetamine and cocaine. 3) To study the role of specific signal transduction mechanisms in behavior mediated by the nucleus accumbens, and how manipulation of such systems may alter the behavioral response to psychostimulants and opiates. For these experiments, intra-accumbens microinjection of bacterial toxins that selectively interfere with G proteins will be carried out in conjunction with studies of motor activity and responding for conditioned reinforcement. Results from this project may contribute to advancement of knowledge in two domains: 1) More detailed understanding of both the behavioral and neurochemical changes induced by psychostimulants and opiates; 2) Further knowledge of the role of specific neural systems within the nucleus accumbens in behavior.