title: Forced opiate withdrawal under anaesthesia augments and prolongs the occurrence of withdrawal signs in rats.
abstract: A newly developed treatment for rapid detoxification of opiate addicts is the use of continuous naloxone/naltrexone administration under general anaesthesia. This method is now introduced in several European countries despite the fact that there is only spare evidence for its effectiveness. Here we report on the assessment of withdrawal symptoms in morphine-dependent rats which received continuous naloxone administration combined with barbiturate anaesthesia. Morphine-dependent rats were implanted with osmotic minipumps filled with either saline or naloxone (delivering 0.5 mg/kg per hour) under barbiturate anaesthesia (lasting for 8 h). Animals were tested daily for the occurrence of withdrawal signs for the subsequent 7 days. All signs of withdrawal which are frequently observed in rats undergoing morphine withdrawal such as body weight loss, diarrhea, writhing, teeth chattering and wet dog shakes were significantly augmented and observed over longer time periods in morphine-dependent animals treated continuously with naloxone versus rats receiving saline. The present study demonstrates that continuous naloxone treatment under anaesthesia worsen and prolongs the detoxification phase in rats. This conflicts with reported clinical observations, and strongly suggests a need for controlled clinical studies before this method enters the everyday clinical routine.
authors.affiliation: Max Planck Institute of Psychiatry, Munich, Germany. spanagel@mpipsykl.mpg.de
authors.forename: R
authors.initials: R
authors.lastname: Spanagel
authors.forename: C
authors.initials: C
authors.lastname: Kirschke
authors.forename: F
authors.initials: F
authors.lastname: Tretter
authors.forename: F
authors.initials: F
authors.lastname: Holsboer
mesh_terms: D000768:Anesthesia, General; D000818:Animals; D008297:Male; D009021:Morphine Dependence / Q000534:rehabilitation*; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009460:Neurologic Examination / Q000187:drug effects; D010424:Pentobarbital; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000175:diagnosis*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D009292:Narcotic Antagonists; D009270:Naloxone; D010424:Pentobarbital