Drugs of Abuse: Neuronal Survival and Signaling

滥用药物：神经元存活和信号传导

• 批准号: 6584460
• 负责人: KRISTA L MOULDER
• 金额: $ 3.83万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-01 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6584460
• 关键词: behavioral /social science research tag; biological signal transduction; brain electrical activity; calcium flux; cell death; drug abuse; electrophysiology; ethanol; excitatory aminoacid; gamma aminobutyrate; glutamate receptor; glutamate transporter; hippocampus; immunocytochemistry; insulinlike growth factor; laboratory rat; membrane channels; neuropharmacology; neurotoxicology; neurotransmitter transport; postdoctoral investigator; potassium; single cell analysis; synapses; synaptogenesis; voltage /patch clamp

DESCRIPTION (provided by applicant): The broadest objective of the proposed research is to characterize the changes in synaptic signaling that accompany increases and decrease in electrical activity. Chronic exposure to drugs of abuse such as ethanol, barbiturates, and benzodiazepines causes a downregulation in electrical activity, which ultimately leads to neuronal death. The goal of Aim 1 is to determine whether this decrease in neuronal activity results in reduced neurotransmitter release because of drug effects on Ca2+ currents, or in enhanced neurotransmitter release through initiation of homeostatic mechanisms. Such changes in synaptic signaling could either lessen or intensify the effects of drugs of abuse on neuronal survival. The goal of Aim 2 is to determine the effects on synaptic signaling caused by mimicking increased electrical activity with K+ depolarization. Preliminary data indicate that depolarization curtails development of glutamatergic synapses, while leaving inhibitory currents intact. Experiments will be conducted to distinguish whether a presynaptic and a postsynaptic mechanism accounts for this effect of K+ on excitatory currents. Both Aim 1 and Aim 2 will utilize whole-cell, patch-clamp techniques in a hippocampal microculture paradigm, which will facilitate examination of synaptic electrophysiology.

描述（由申请人提供）：