Electrophysiological and electrochemical studies of addictive drugs

National Institute On Drug Abuse

Investigators

Linked publications & trials

Abstract

In this year, we conducted three sub-projects. First, we employed oxygen sensors coupled with high-speed amperometry to evaluate fluctuations in oxygen levels in the brain and periphery induced by fentanyl and the effects of naloxone delivered both before and at different time after fentanyl injections. 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, had minimal blocking effects in the brain when delivered at >10 min after fentanyl. In the second project, we employed electrochemical technology to examine the pattern of brain oxygen changes induced by ketamine and its co-administration with fentanyl. In this study we showed that ketamine used alone increases brain oxygen levels and potentiate oxygen responses induced by fentanyl. In the third project we examined brain oxygen responses induced by xylazine, a veterinary analgesic which is often co-used with fentanyl and heroin. We found, that xylazine used alone moderately decreases brain oxygen levels. When used together with fentanyl or heroin, the addition of xylazine increased both the amplitude and duration of drug-induced oxygen decreases. Currently, we are working to test possible therapeutic strategies to attenuate the hypoxic effects of opioid drugs contaminated by xylazine.