Severe deficit in brain reward function associated with fentanyl withdrawal in rats.

BACKGROUND: During the last decade, there has been a strong increase in the use of the mu-opioid receptor agonist fentanyl. The aim of these studies was to investigate the effects of fentanyl withdrawal on brain reward function and somatic withdrawal signs. METHODS: Fentanyl and saline were chronically administered via minipumps. An intracranial self-stimulation procedure was used to provide a measure of brain reward function. Somatic signs were recorded from a checklist of opioid abstinence signs. RESULTS: The opioid receptor antagonist naloxone induced a dose-dependent elevation in brain reward thresholds and somatic withdrawal signs in fentanyl-treated rats. Discontinuation of fentanyl administration resulted in a time-dependent elevation of brain reward thresholds and somatic withdrawal signs. CONCLUSIONS: These findings indicate that fentanyl withdrawal is associated with affective and somatic withdrawal signs. The severity of the deficit in brain reward function in this animal model suggests that affective fentanyl withdrawal symptoms may be a strong deterrent to abstinence.

Fentanyl abuse and dependence: further evidence for second hand exposure hypothesis.

We have proposed a novel hypothesis regarding the potential role of occupational or second-hand exposure in physician substance use, abuse, and addiction. While only 5.6% of licensed physicians in Florida are anesthesiologists, nearly 25% of physicians followed for substance abuse/dependence are anesthesiologists. When we sort by drug of choice, anesthesiologists have more opioid abuse and dependence than other physicians and appropriate controls. Abuse of one opioid, fentanyl, appears to be increasing and has been noted among the State of Florida's causes of opioid deaths. Fentanyl and sufentanyl are commonly administered highly potent opioid analgesics, as much as 80-800 times as potent as morphine. We have recent data from the State of Florida impaired physicians database, which has allowed us to categorize all fentanyl abusing and/ or dependent physicians. Just knowing that a physician abuses fentanyl gives you a good clue as to their specialty; 75% are anesthesiologists! While drug abuse researchers, oncologists and others who handle drugs of abuse everyday, have no greater incidence of opioid abuse or dependence, anesthesiologists are at the top of every list. Can this be due to just access and stress? We have proposed an alternative hypothesis of second hand exposure. To test this hypothesis, we developed a sensitive LC/MS/MS assay to measure the intravenous anesthetic and analgesic agents, propofol and fentanyl in air. Not only did we detect propofol and fentanyl in cardiovascular surgery operating room air, we also found the highest concentrations were close to the patient's mouth where anesthesiologists work for hours. Like tobacco, second hand opioid exposure can sensitize and change the brain making abuse, dependence and behavioral disorders more likely. Thus environmental exposure and sensitization may be an important risk factor in physician addiction. Second hand exposure may affect treatment outcome and explain anesthesiologist's inability to return to work in the operating room. We are developing an animal model for second hand exposure and additional studies of the operating room and cardiac anesthesiologists are underway.