Electrophysiological and electrochemical studies of addictive drugs

National Institute On Drug Abuse

Investigators

Linked publications, trials & patents

Abstract

In this year, we conducted two sub-projects, using oxygen sensors coupled with high-speed amperometry in awake freely-moving rats. First, we examined fluctuations in oxygen levels in the brain and periphery induced by fentanyl at different doses and compared brain oxygen responses induced by intravenous and intraperitoneal fentanyl administration. This study revealed that intravenous fentanyl has biphasic effects on brain oxygen, with rapid, strong but relatively short oxygen decrease (hypoxia) followed by weaker and more prolonged increase (hyperoxia). Due to this pattern, naloxone, which is highly effective to block fentanyl's effects when delivered before fentanyl exposure, but has a weak therapeutic potential when used after fentanyl exposure started more than 10 min after fentanyl. We also found that fentanyl at low doses (<3-5 ug/kg, iv)increases brain oxygen levels. In the second project we examined how brain oxygen responses are affected by naloxone and naloxone-methiodide, naloxone's analog which cannot enter brain tissue. This study clarified the role of peripheral vs. central actions of fentanyl.