Dopamine regulates drug and social reward interactions

多巴胺调节药物和社会奖励相互作用

• 批准号: 6912198
• 负责人: ZUOXIN WANG
• 金额: $ 25.14万
• 依托单位: FLORIDA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6912198
• 关键词: amphetamines; autoradiography; behavior test; behavioral /social science research tag; behavioral habituation /sensitization; conditioning; dopamine; dopamine receptor; drug addiction; gender difference; high performance liquid chromatography; in situ hybridization; microdialysis; neural plasticity; neuropsychology; neuroregulation; nucleus accumbens; preference; psychopharmacology; reinforcer; sex behavior; social behavior; species difference; stereotaxic techniques; vole

DESCRIPTION (provided by applicant): It is believed that drugs of abuse usurp neural circuitry that initially evolved to mediate behavioral processes essential for fitness. Therefore, the take over of this circuitry by drugs of abuse usually exerts powerful control over the behavior and this is a tremendous problem for many humans. One important factor contributing to drug abuse is social environment. It has been suggested that social attachments formed in adulthood may have significant impact on drug addictions. Unfortunately, investigation into this topic is very limited partially because the vast majority of addiction research is conducted on traditional laboratory rats and mice that do not form adult-adult social attachments. Here we propose a novel line of research using a unique animal model to address fundamental questions regarding the interaction of social and drug reward and the underlying neural mechanisms. The monogamous prairie vole (Microtus ochrogaster) displays mating-induced pair bonding between mates, and this behavior is mediated by dopamine (DA) in the nucleus accumbens (NAcc). Recently, we also found that the prairie vole displays amphetamine (AMPH)-induced conditioned place preference (CPP) and pre-treatment of the DA receptor antagonist blocked this behavior. As natural reward and maladaptive drug reward are both regulated by DA, we hypothesized that these overlapping neural mechanisms will result in behavioral and neurobiological interactions between pair bonding and drug addiction. Here, we propose four studies by taking advantage of the vole model to systematically address interactions between pair bonding and drug reward and to study NAcc DA involvement in the regulation of such interactions. In Specific Aim 1, we will firmly establish the vole model for drug reward by performing detailed dose response curves for AMPH induced CPP and behavioral sensitization. In Specific Aim 2, we will examine NAcc DA involvement in AMPH reward. In Specific Aim 3, we will study behavioral interactions between pair bonding and AMPH reward. In Specific Aim 4, we will investigate the role of NAcc DA in the regulation of interactions between pair bonding and AMPH reward. Successful completion of these studies will further our understanding of behavioral and neurobiological interactions between social and drug reward, and such findings will have the potential to facilitate behavioral and neuropharmacological interventions that may aid addiction prevention.

描述（由申请人提供）：据信滥用药物会侵占最初进化为调节健身所必需的行为过程的神经回路。因此，滥用药物接管该回路通常会对行为产生强大的控制，这对许多人来说是一个巨大的问题。社会环境是导致药物滥用的重要因素之一。有人认为，成年后形成的社会依恋可能对毒瘾产生重大影响。不幸的是，对这个主题的研究非常有限，部分原因是绝大多数成瘾研究是在不形成成年社会依恋的传统实验室大鼠和小鼠上进行的。在这里，我们提出了一种新颖的研究路线，使用独特的动物模型来解决有关社会和药物奖励相互作用以及潜在神经机制的基本问题。 一夫一妻制的草原田鼠（Microtus ochrogaster）在配偶之间表现出交配诱导的配对结合，这种行为是由伏隔核（NAcc）中的多巴胺（DA）介导的。最近，我们还发现草原田鼠表现出安非他明（AMPH）诱导的条件性位置偏好（CPP），而DA受体拮抗剂的预处理可以阻止这种行为。由于自然奖励和适应不良药物奖励均受 DA 调节，我们假设这些重叠的神经机制将导致配对关系和药物成瘾之间的行为和神经生物学相互作用。在这里，我们提出了四项研究，利用田鼠模型来系统地解决配对关系和药物奖励之间的相互作用，并研究 NAcc DA 参与此类相互作用的调节。在具体目标 1 中，我们将通过对 AMPH 诱导的 CPP 和行为致敏进行详细的剂量反应曲线，牢固地建立药物奖励的田鼠模型。在具体目标 2 中，我们将研究 NAcc DA 对 AMPH 奖励的参与。在具体目标 3 中，我们将研究结对关系和 AMPH 奖励之间的行为相互作用。在具体目标 4 中，我们将研究 NAcc DA 在调节配对结合和 AMPH 奖励之间相互作用中的作用。这些研究的成功完成将进一步我们对社会和药物奖励之间的行为和神经生物学相互作用的理解，这些发现将有可能促进行为和神经药理学干预，从而有助于预防成瘾。