Abstract
Methadone HCl was administered daily to four stump-tailed macaques. The animals' sleep was periodically examined throughout a year of methadone maintenance and, in two animals, during eight months of withdrawal. REM sleep was substantially decreased by methadone treatment and gradually returned to predrug values over a 6-to 8-month period of maintenance. Measures of non-REM sleep and awakenings showed similar disruption with no return to predrug values. These changes were not correlated with alterations in plasma-methadone concentrations. REM sleep rebound occurred temporarily upon drug with-drawal in two animals, but no consistent sleep disruption was apparent during the subsequent eight months. Contrary to some suggestions, therefore, tolerance to the sleep-disruptive effects of the drug may be specific and incomplete, and extended REM rebound upon withdrawal is not a universal response.
Similar content being viewed by others
References
Agnew, H. W., Wilse, W. B., Williams, R. L.: The first night effect and study of sleep. Psychophysiology 2, 263–266 (1966)
Berkowitz, B. A.: The relationship of pharmacokinetics to pharmacological activity: morphine, methadone and naloxone. Clin. Pharmacokinetics 1, 219–230 (1976)
Bert, J., Pegram, V.: Sleep and environment. In: Medical primatology, E. I. Goldsmith and J. Moor-Jankowski, eds., pp. 244–249. Basel: Karger 1972
Bert, J.: Basic factors of sleep organization in primates. In: Sleep: physiology, biochemistry, psychology, pharmacology, clinical implications, W. P. Koella and P. Levin, eds., Basel: Karger 1973
Blachly, P. H., David, N. A., Irwin, S.: L-Alpha acelylmethadol (LAAM): comparison of laboratory findings, electroencephalograms, and Cornell Medical Index of patients stabilized on LAAM with those on methadone. Fourth Nat. Conf. Methadone Treatment Proceedings, Nat. Assn. Prevention of Addiction to Narcotics, New York, pp. 203–205 (1972)
Clouet, D. H., Iwatsubo, K.: Mechanisms of tolerance to and dependence on narcotic analgesic drugs. Annu. Rev. Pharmacol. 15, 49–71 (1975)
Cochin, J., Kornetsky, C.: Development and loss of tolerance to morphine in the rat after single and multiple injections. J. Pharmacol. Exp. Ther. 145, 1–10 (1964)
Colasanti, B., Kirchman, A., Khazan, N.: Changes in the electroencephalogram and REM sleep time during morphine abstinence in pellet-implanted rats. Res. Commun. Chem. Path. Pharm. 12, 163–172 (1975)
Downs, D. A., Thomas, D. J., Braude, M. C.: Chronic effects of acetylmethadol and methadone in rhesus monkeys. Life Sci. 21, 719–726 (1977)
Duncan, D. B.: Multiple range and multiple F tests. Biometrics 11, 1–42 (1955)
Echols, S. D., Jewett, R. E.: Effects of morphine on sleep in the cat. Psychopharmacologia (Berl.) 24, 435–448 (1972)
Eibergen, R. D., Carlson, K. R.: Dyskinesis elicited by methamphetamine: susceptibility of former methadone-consuming monkeys. Science 190, 588–589 (1975)
Gelfand, D. M., Hartmann, D. P.: Child behavior: analysis and therapy. New York: Pergamon 1975
Gottman, J. M.: N-of-one and N-of-two research in psychotherapy. Psychol. Bull. 80, 93–105 (1973)
Hartmann, E. L.: The functions of sleep. New Haven: Yale University Press 1973
Henderson, A., Nemes, G., Gordon, N. B., Ross, L.: Sleep and narcotic tolerance. Psychophysiology 7, 346–347 (1970)
Horns, W. H., Rado, M., Goldstein, A.: Plasma levels and symptom complaints in patients maintained on daily dosage of methadone hydrochloride. Clin. Pharmacol. Ther. 17, 636–649 (1975)
Irwin, S., Seevers, M. H.: Altered response to drugs in the post addict (Macaca mulatta). J. Pharmacol. Exp. Ther. 116, 31–32 (1956)
Kay, D. C.: Human sleep and EEG through a cycle of methadone dependence. Electroencephalogr. Clin. Neurophysiol. 38, 35–43 (1975)
Khazan, N.: The implication and significance of EEG and sleepawake activity in the study of experimental drug dependence on morphine. In: Methods in narcotic research, S. Ehrenpreis and A. Neidle, eds. New York: Dekker 1975
Klingman, G. I., Maynert, E. W.: Tolerance to morphine. III. Effects on catecholamines in the heart, intestine and spleen. J. Pharmacol. Exp. Ther. 135, 300–305 (1962)
Krikpke, D. F., Reite, M. L., Pegram, G. V., Stephens, L. M., Lewis, O. F.: Nocturnal sleep in rhesus monkeys. Electroencephalogr. Clin. Neurophysiol. 24, 582–586 (1968)
Laska, F. J., Fennessy, M. R.: Physical dependence in the rat induced by slow release morphine: dose response, time course and brain biogenic amines. Clin. Exp. Pharmacol. Physiol. 3, 587–598 (1976)
Lewis, S. A., Oswald, I., Evans, J. I., Arkindele, M. O., Tompsett, S. L.: Heroin and human sleep. Electroencephalogr. Clin. Neurophysiol. 28, 374–381 (1970)
Lewis, J. F., Lewis, S. A., Tinker, M.: Chlormethazole, sleep, and drug withdrawal. Psych. Med. 2, 239–247 (1972)
Martin, W. R., Wikler, A., Eades, C. G., Pescor, F. T.: Tolerance to and physical dependence on morphine in rats. Psychopharmacologia (Berl.) 4, 247–260 (1963)
Martin, W. R., Jasinski, D. R., Sapira, J. D., Flanary, H. G., Kelley, O. H., Thompson, A. K., Logan, C. R.: The respiratory effects of morphine during a cycle of dependence. J. Pharmacol. Exp. Ther. 162, 182 (1968)
Martin, W. R., Jasinski, D. R.: Physiological parameters of morphine dependence in man: tolerance, early abstinence, protracted abstinence. J. Psychiatr. Res. 7, 9–17 (1969)
Meyers, J. L.: Fundamentals of experimental design. Boston: Allyn and Bacon 1969
Misra, A. L., Vardy, J., Block, R., Mulé, G. E.: Pharmacokinetics and metabolism of (-)-α-(2-H) acetylmethadol (LAAM) in the monkey: evidence for a new metabolite. J. Pharm. Pharmacol. 28, 316–318 (1976)
Oswald, I., Evans, J. L., Lewis, S. A.: Addictive drugs cause suppression of paradoxical sleep and withdrawal rebound. In: Scientific basis of drug dependence, H. Steinberg, ed., pp. 243–257. London: Churchill 1969
Rechtschaffen, A., Kales, A., eds.: A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects. Los Angeles: Brain Information Service/Brain Research Institute, Univer. California, Los Angeles, p. 8 1973
Reite, M., Stynes, A. J., Vaughn, L., Pauley, J. D., Short, R. A.: sleep in infant monkeys: normal values and behavioral correlates. Physiol. Behav. 16, 245–251 (1976)
Satoh, M., Zieglgansberger, W., Herz, A.: Actions of opiates upon single unit activity in the cortex of naive and tolerant rats. Brain Res. 115, 99–110 (1976)
Shearer, D. E., Snyder, E. W., Beck, E. C., Dustman, R. E.: A miniature, readily available electrode pedestal for recording cerebral and other electrophysiological activity from several species. Lab. Anim. Sci. 26, 630–632 (1976)
Sloan, J. W., Brooks, J. W., Eisenman, A. J., Martin, W. R.: The effect of addiction to and abstinence from methandone on rat tissue catecholamines and serotonin levels. Psychopharmacologia (Berl.) 4, 261–270 (1963)
Snider, R. S., Lee, J. E.: A stereotaxic atlas of the monkey brain. Chicago: University of Chicago Press 1961
Snyder, E. W., Dustman, R. E., Straight, R. C., Wayne, A. W., Beck, E. C.: Sudden toxicity of methadone in monkeys: behavioral and electrophysiological evidence. Pharmacol. Biochem. Behav. 6, 87–92 (1977)
Snyder, E. W., Dustman, R. E., Johnson, R. L.: Sawtooth waves: concomitants of rapid eye movement sleep in monkeys. Electroencephalogr. Clin. Neurophysiol. 45, 111–113 (1978)
Wikler, A., Pescor, F. T.: Classical conditioning of a morphine abstince phenomenon, reinforcement of opioid-drinking behavior and ‘relapse’ in morphine addicted rats. Psychopharmacologia (Berl.) 10, 255 (1967)
Zimmermann, E., Branch, B., Newman Taylor, A., Young, J., Pang, C. N.: Long lasting effects of prepuberal administration of morphine in adult rats. In: Narcotics and the hypothalamus, E. Zimmermann and R. George, eds., pp. 183–196. New York: Raven 1974
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Snyder, E.W., Dustman, R.E. & Beck, E.C. Sustained ingestion of methadone and the sleep of monkeys. Psychopharmacology 60, 29–34 (1978). https://doi.org/10.1007/BF00429175
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00429175