Featured Paper of the Month – May 2018.
Fentanyl is a potent synthetic opioid used clinically to treat pain and as a general anesthetic. Recently, fentanyl has emerged as a recreational drug and its overdose has been linked to numerous deaths in the US. To better understand how fentanyl affects the brain, we used electrochemical techniques in rats and examined the effect of intravenous fentanyl on oxygen and glucose levels in the nucleus accumbens, a brain region implicated in reward and addiction. Oxygen and glucose are metabolism-related substances that must be constantly supplied to the brain for it to function properly. We found that at doses corresponding to human consumption, fentanyl caused brain oxygen levels to drop within seconds and subsequently glucose levels to increase. By measuring oxygen in a highly-vascularized region under the skin, we determined that the fentanyl-induced brain hypoxia is caused by the drop of blood oxygen levels resulting from drug-induced breathing depression. Diminished breathing also leads to carbon dioxide accumulation, which in turn causes vasodilation of blood vessels in the brain allowing enhanced glucose entry into the brain. Compared to other opioids, such as heroin or morphine, fentanyl doses required to cause hypoxia were very low, which highlights the danger when mistakenly consuming fentanyl instead of heroin or heroin that was contaminated with fentanyl.
Neuropsychopharmacology, 43 (4), pp. 810–819, 0000, ISSN: 1740-634X (Electronic); 0893-133X (Linking).