Activating and Inhibitory PKA mutations in drug abuse

药物滥用中的激活和抑制 PKA 突变

• 批准号: 7123429
• 负责人: JOHN P JONES
• 金额: $ 4.99万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-24 至 2007-09-23
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7123429
• 关键词: artificial chromosomes; behavior test; behavioral /social science research tag; craving; dopamine receptor; drug abuse; drug addiction; enzyme activity; gene expression; gene mutation; genetically modified animals; laboratory mouse; pathologic process; phosphorylation; postdoctoral investigator; protein kinase A; protein structure function; psychobiology; psychopathology; receptor expression; recombinase; relapse /recurrence; self medication; substance abuse related behavior

DESCRIPTION (provided by applicant): This proposal will test the hypothesis that acute and chronic changes in the ability to activate PKA dependent phosphorylation underlie addictive behaviors and involves generating two constructs that will allow expression of CRE recombinase in a cell specific and temporal fashion. This recombinase will be used to turn on activating and inhibitory protein kinase A (PKA) mutations in dopamine D1 or D2 receptor expressing cells in order to investigate the effects of altered kinase activity on drug seeking behavior and relapse. We hypothesize that mutations that activate PKA activity in D1 receptor expressing cells will inhibit self-administration and relapse of drug taking behavior while mutations that inhibit PKA activity in D2 expressing cells will enhance drug seeking behavior and induce relapse. A detailed understanding of the molecular changes that occur in specific brain regions during chronic drug exposure that underlie the subsequent behavioral changes may provide novel therapeutic targets for pharmacological intervention.

描述（由申请人提供）：