Cardiovascular Changes Induced By Drugs of Abuse

滥用药物引起的心血管变化

• 批准号: 7966743
• 负责人: Steven Goldberg
• 金额: $ 14.15万
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 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/7966743
• 关键词: Adenosine; Adverse effects; Agonist; Behavior; Behavioral; Caffeine; Cardiovascular system; Cocaine; Drug usage; Glutamates; Goals; Heart Rate; Implant; Individual; Injection of therapeutic agent; Methamphetamine; Microdialysis; Nucleus solitarius; Pharmaceutical Preparations; Play; Process; Purinergic P1 Receptors; Rattus; Relapse; Research; Role; Safety; Self Administration; Site; drug of abuse

Adenosine plays a role in the behavioral effects of caffeine, one of the most widely used drugs in the world. We have previously shown that adenosine A2A agonists can increase heart rate in rats, an effect that appears to be medicated by CNS adenosine receptors. The site of action for this effect has been hypothesized to be the nucleus tractus solitarius (NTS). To investigate this possibility further, we previously implanted microdialysis probes in the NTS and administered the adenosine agonist CGS 21680. CGS 21680 produced an increase in the level of glutamate in the NTS, while the adenosine A2A antagonist MSX-3 produced a decrease of glutatmate, suggesting a tonic level of control by adenosine. The combination of CGS 21680 and MSX-3 produced no change in glutatmate. We are currently investigating whether the injection of CGS 21680 into the NTS will produce cardiovascular effects similar to systemic administration in an effort to confirm that the NTS regulates these effects of adenosine agonists.

腺苷在咖啡因的行为效应中起着作用，咖啡因是世界上使用最广泛的药物之一。我们之前已经证明，腺苷A2A激动剂可以增加大鼠的心率，这种作用似乎是通过中枢神经系统的腺苷受体来实现的。这种效应的作用部位被假设为孤束核(NTS)。为了进一步研究这种可能性，我们先前在NTS植入了微透析探针，并给予腺苷激动剂CGS 21680。CGS 21680使NTS中谷氨酸水平升高，而腺苷A2A拮抗剂Msx-3使谷氨酸水平降低，提示腺苷控制的紧张性水平。CGS 21680和MSX-3的组合没有引起谷氨酸的变化。我们目前正在研究将CGS 21680注入NTS是否会产生类似于全身给药的心血管效应，以努力证实NTS调节腺苷激动剂的这些效应。