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: 7028962
• 负责人: ZUOXIN WANG
• 金额: $ 24.51万
• 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/7028962
• 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，滥用的药物篡夺了最初进化以介导适应性必不可少的行为过程的神经回路。因此，滥用药物对这一电路的接管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。导致药物滥用的一个重要因素是社会环境。已经提出，成年后形成的社会依恋可能会对吸毒成瘾产生重大影响。不幸的是，对该主题的调查在很大程度上是有限的，因为绝大多数成瘾研究是针对不构成成人成人社会依恋的传统实验室大鼠和小鼠进行的。在这里，我们提出了一项新的研究系列，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的神经机制的基本问题。 一夫一妻制的草原vole（Microtus ochrogaster）显示了伴侣之间的交配诱导的对键，并且这种行为是由伏源（NACC）中多巴胺（DA）介导的。最近，我们还发现，草原沃尔（Prairie Vole）显示了苯丙胺（AMPH）诱导的条件位置偏好（CPP），而DA受体拮抗剂的预处理阻止了这种行为。由于自然奖励和适应不良的药物奖励均受DA的调节，因此我们假设这些重叠的神经机制将导致成对粘结与药物成瘾之间的行为和神经生物学相互作用。在这里，我们通过利用Vole模型来系统地解决配对键和药物奖励之间的相互作用，并研究NACC DA在调节此类相互作用中的参与，从而提出四项研究。在特定目标1中，我们将通过对AMPH诱导的CPP和行为敏化的详细剂量反应曲线进行详细的剂量反应曲线来牢固建立药物奖励模型。在特定目标2中，我们将研究NACC DA参与AMPH奖励。在特定的目标3中，我们将研究成对键和AMPH奖励之间的行为相互作用。在特定的目标4中，我们将研究NACC DA在调节配对键和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了解社会和药物奖励之间的行为和神经生物学相互作用，这些发现将有可能促进行为和神经药理学干预措施，这可能有助于预防成瘾。