Forced opiate withdrawal under anaesthesia augments and prolongs the occurrence of withdrawal signs in rats. 1998

R Spanagel, and C Kirschke, and F Tretter, and F Holsboer
Max Planck Institute of Psychiatry, Munich, Germany. spanagel@mpipsykl.mpg.de

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.

UI MeSH Term Description Entries
D008297 Male Males
D009021 Morphine Dependence Strong dependence, both physiological and emotional, upon morphine. Morphine Abuse,Morphine Addiction,Abuse, Morphine,Addiction, Morphine,Dependence, Morphine
D009270 Naloxone A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. MRZ 2593-Br,MRZ-2593,Nalone,Naloxon Curamed,Naloxon-Ratiopharm,Naloxone Abello,Naloxone Hydrobromide,Naloxone Hydrochloride,Naloxone Hydrochloride Dihydride,Naloxone Hydrochloride, (5 beta,9 alpha,13 alpha,14 alpha)-Isomer,Naloxone, (5 beta,9 alpha,13 alpha,14 alpha)-Isomer,Narcan,Narcanti,Abello, Naloxone,Curamed, Naloxon,Dihydride, Naloxone Hydrochloride,Hydrobromide, Naloxone,Hydrochloride Dihydride, Naloxone,Hydrochloride, Naloxone,MRZ 2593,MRZ 2593 Br,MRZ 2593Br,MRZ2593,Naloxon Ratiopharm
D009292 Narcotic Antagonists Agents inhibiting the effect of narcotics on the central nervous system. Competitive Opioid Antagonist,Narcotic Antagonist,Opioid Antagonist,Opioid Antagonists,Opioid Receptor Antagonist,Opioid Reversal Agent,Competitive Opioid Antagonists,Opioid Receptor Antagonists,Opioid Reversal Agents,Agent, Opioid Reversal,Agents, Opioid Reversal,Antagonist, Competitive Opioid,Antagonist, Narcotic,Antagonist, Opioid,Antagonist, Opioid Receptor,Antagonists, Competitive Opioid,Antagonists, Narcotic,Antagonists, Opioid,Antagonists, Opioid Receptor,Opioid Antagonist, Competitive,Opioid Antagonists, Competitive,Receptor Antagonist, Opioid,Receptor Antagonists, Opioid,Reversal Agent, Opioid,Reversal Agents, Opioid
D009460 Neurologic Examination Assessment of sensory and motor responses and reflexes that is used to determine impairment of the nervous system. Examination, Neurologic,Neurological Examination,Examination, Neurological,Examinations, Neurologic,Examinations, Neurological,Neurologic Examinations,Neurological Examinations
D010424 Pentobarbital A short-acting barbiturate that is effective as a sedative and hypnotic (but not as an anti-anxiety) agent and is usually given orally. It is prescribed more frequently for sleep induction than for sedation but, like similar agents, may lose its effectiveness by the second week of continued administration. (From AMA Drug Evaluations Annual, 1994, p236) Mebubarbital,Mebumal,Diabutal,Etaminal,Ethaminal,Nembutal,Pentobarbital Sodium,Pentobarbital, Monosodium Salt,Pentobarbitone,Sagatal,Monosodium Salt Pentobarbital
D000768 Anesthesia, General Procedure in which patients are induced into an unconscious state through use of various medications so that they do not feel pain during surgery. Anesthesias, General,General Anesthesia,General Anesthesias
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013375 Substance Withdrawal Syndrome Physiological and psychological symptoms associated with withdrawal from the use of a drug after prolonged administration or habituation. The concept includes withdrawal from smoking or drinking, as well as withdrawal from an administered drug. Drug Withdrawal Symptoms,Withdrawal Symptoms,Drug Withdrawal Symptom,Substance Withdrawal Syndromes,Symptom, Drug Withdrawal,Symptom, Withdrawal,Symptoms, Drug Withdrawal,Symptoms, Withdrawal,Syndrome, Substance Withdrawal,Syndromes, Substance Withdrawal,Withdrawal Symptom,Withdrawal Symptom, Drug,Withdrawal Symptoms, Drug,Withdrawal Syndrome, Substance,Withdrawal Syndromes, Substance
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor

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