Contribution of NMDA NR2B subunit to risky choice and economic demand for cocaine

点击翻译按钮获取中文摘要

Project Summary/Abstract Risky choice is one facet of impulsivity that is observed in several psychiatric disorders, including substance use disorders. Understanding the shared neurobiology of risk-taking behavior and drug abuse is important for designing effective pharmacotherapies for individuals that are at risk for developing substance use disorders. The neurotransmitter glutamate is considered to be involved in drug addiction, and recent research has shown that the N-methyl-D-aspartate (NMDA) glutamate receptor is involved in risky choice. Considering NR2B- selective antagonists lack the psychotomimetic side effects observed with NMDA receptor channel blockers (such as MK-801 and ketamine), these drugs may provide a novel therapeutic approach to treating individuals predisposed to engaging in risky behaviors. Using the risky decision task (RDT), in which rats choose between a small, safe reward and a large, risky reward (i.e., paired with foot shock), we recently found that the GluN2B-selective antagonist Ro 63-1908 decreases risky choice, but only in male rats. We are currently determining if blocking NR2B-containing NMDA receptors is efficacious in attenuating cocaine self-administration in rats displaying increased risky choice (Specific Aim 2 of grant). Another goal of the proposal is to determine if cocaine exposure differentially alters NR2B subunit distribution (via receptor autoradiography) in high and low risk-taking rats and to determine if Ro 63-1908 can reverse cocaine-induced alterations in NR2B subunit distribution (Specific Aim 3). Zachary will assist with data collection and data analysis. Specifically, he will work on research related to Specific Aims 2 and 3 of Dr. Yates’ R15 grant. Briefly, Zachary will learn to handle and weigh rats, test rats in a cocaine self-administration paradigm, deliver subcutaneous injections, record and analyze data, and perform animal husbandry. Zachary will read articles related to the research he will be conducting during the internship, and he will meet regularly with Dr. Yates and his other students to discuss this research, as well as progress in the experiment. In addition to drug self- administration, Zachary will learn to section brains for receptor autoradiography experiments. As required, Zachary will work 40 hours each week for 8 weeks during the summer.