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 after fentanyl injections. While hypoxic effects of drugs are usually assessed by using oximetry and plethysmography, we developed technology that allowed us to examine real-time changes of oxygen in the brain. This study revealed that intravenous fentanyl has biphasic effects in the brain, with rapid, strong but relatively short oxygen decrease (hypoxia) followed by weaker and more prolonged increase. 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 contrast, at 1oth min after fentanyl naloxone was effective to attenuate hypoxia in the periphery. In the second project, we employed this technology to examine the pattern of brain oxygen changes during glucose-drinking behavior, a simple model of learned goal-directed behavior. In this study we found rapid and strong brain oxygen increase following exposure of trained rats to a glucose-containing cup. This increase was maintained and slightly decreased during subsequent drinking behavior. In the third project, which is in progress now, we examined brain oxygen responses induced by ketamine, a psychoactive drug used recreationally. Since drug users often combine ketamine with opioid drugs, we also examined how this drug combination affects brain oxygen responses induced by fentanyl. Our preliminary data suggest that ketamine strongly potentiates fentanyl-induced brain hypoxia, making this combined drug exposure much more dangerous than that induced by each drug alone.