Naltrexone modulates tumor response in mice with neuroblastoma.

Naltrexone, an opiate antagonist, had both stimulatory and inhibitory effects, depending on the dosage, on the growth of S20Y neuroblastoma in A/Jax mice. Daily injections of 0.1 milligram of naltrexone per kilogram of body weight, which blocked morphine-induced analgesia for 4 to 6 hours per day, resulted in a 33 percent tumor incidence, a 98 percent delay in the time before tumor appearance, and a 36 percent increase in survival time. Neuroblastoma-inoculated mice receiving 10 milligrams of naltrexone per kilogram, which blocked morphine-induced analgesia for 24 hours per day, had a 100 percent tumor incidence, a 27 percent reduction in the time before tumor appearance, and a 19 percent decrease in survival time. Inoculation of neuroblastoma cells in control subjects resulted in 100 percent tumor incidence within 29 days. These results show that naltrexone can modulate tumor response and suggest a role for the endorphin-opiate receptor system in neuro-oncogenic events.

[1]  J. Meites,et al.  Effects of naloxone, morphine and methionine enkephalin on serum prolactin, luteinizing hormone, follicle stimulating hormone, thyroid stimulating hormone and growth hormone. , 1977, Life sciences.

[2]  I. Zagon,et al.  Naloxone prolongs the survival time of mice treated with neuroblastoma. , 1981, Life sciences.

[3]  E. Fonkalsrud,et al.  An experimental model for the therapy of mouse neuroblastoma. , 1973, Journal of pediatric surgery.

[4]  R. Collins,et al.  Enhanced analgesic effects of morphine after chronic administration of naloxone in the rat. , 1978, European journal of pharmacology.

[5]  I. Zagon,et al.  Heroin prolongs survival time and retards tumor growth in mice with neuroblastoma , 1981, Brain Research Bulletin.

[6]  J. Schneider,et al.  Effects of methadone hydrochloride on the growth of organotypic cerebellar cultures prepared from methadone-tolerant and control rats. , 1976, The Journal of pharmacology and experimental therapeutics.

[7]  C. Pert,et al.  Naltrexone reduces weight gain, alters “β-endorphin”, and reduces insulin output from pancreatic islets of genetically obese mice , 1980, Peptides.

[8]  M. Nirenberg,et al.  A Neuroblastoma × Glioma Hybrid Cell Line with Morphine Receptors , 1974 .

[9]  T. Slotkin,et al.  Effects of maternal methadone administration on ornithine decarboxylase in brain and heart of the offspring: relationships of enzyme activity to dose and to growth impairment in the rat. , 1980, Life sciences.

[10]  R. Collins,et al.  Chronic naloxone results in prolonged increases in opiate binding sites in brain. , 1978, European journal of pharmacology.

[11]  I. Zagon,et al.  The effects of different schedules of methadone treatment on rat brain development , 1977, Experimental Neurology.

[12]  M. Crofford,et al.  Inhibition of growth in young mice treated with d,1-methadone. , 1977, European journal of pharmacology.

[13]  W. Geber,et al.  Action of naloxone on the interferon-lowering activity of morphine in the mouse. , 1976, Pharmacology.

[14]  R. Zukin,et al.  Naltrexone-induced opiate receptor supersensitivity , 1982, Brain Research.