CENTRAL NERVOUS SYSTEM GLUTAMATE AND C-FOS MRNA IN ALCOHOL WITHDRAWAL

酒精戒断中中枢神经系统谷氨酸和 C-FOS mRNA

• 批准号: 3801974
• 负责人: P MORGAN
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3801974
• 关键词: NMDA receptors; alcoholism /alcohol abuse; brain; cell growth regulation; drug withdrawal; excitatory aminoacid; gene expression; glutamates; inhibitor /antagonist; laboratory rat; messenger RNA; nucleic acid probes; oncogenes

Activation of brain cells by receptor activation or changes in ion flux can result in the rapid and transient expression of certain key genes, such as the c-fos gene, which are capable of controlling and orchestrating the transcription of a large number of dependent genes. Such altered gene expression may underlie normal, as well as pathophysiological, long term changes in cell function. We have mapped the expression of the c-fos gene in rat brain during alcohol intoxication and withdrawal and have identified several brain structures in which expression is increased during alcohol withdrawal. We have demonstrated that the regional expression of c-fos mRNA observed during alcohol withdrawal can be mimicked by acute administration of N-methyl-D-aspartic acid (NMDA) and stereospecifically blocked by the NMDA receptor/ionophore blocker, MK-801. We have also demonstrated that levels of glutamate (an endogenous ligand for NMDA receptors), but not other excitatory and inhibitory amino acid putative neurotransmitters, are increased in the brain during alcohol withdrawal. Current research is focused on pharmacologically characterizing the increased expression of c-fos mRNA observed during alcohol withdrawal. In addition we are developing and screening DNA probes for other second messenger-dependent genes which may exhibit altered expression during alcohol intoxication or withdrawal.

通过受体激活或离子通量的变化可以激活脑细胞