Endogenous Opiate Systems May Modulate Learning and Memory

  • Gayle A. Olson
  • Richard D. Olson
  • Abba J. Kastin
  • David H. Coy


It is becoming increasingly realized that the endogenous opiate peptides have numerous effects on a wide range of behaviors and physiological conditions. Some of these effects may reflect the multiple physiological roles these peptides might play other than the ones related to pain perception; these additional roles may, in fact, be of more importance to the organism than the antinociceptive function with which the peptides were originally associated. Learning and memory processes might represent important functions modulated by the peptides.


Passive Avoidance Active Avoidance Senile Dementia Opiate Receptor Retrograde Amnesia 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Botticelli, L. J., and Wurtman, R. J., 1979, Beta-endorphin administration increases hippocampal acetylcholine levels, Life Sci. 24:1799.PubMedCrossRefGoogle Scholar
  2. Broekkamp, C. L., Phillips, A. G., and Cools, A. R., 1979, Facilitation of self-stimulation behavior following intracerebral microinjections of opioids into the ventral tegmental area, Pharmacol. Biochem. Behav. 11:289.PubMedCrossRefGoogle Scholar
  3. Castellano, C., 1975, Effects of morphine and heroin on discrimination learning and consolidation in mice, Psychopharmacologia 42:235.PubMedCrossRefGoogle Scholar
  4. Castellano, C., 1981, Strain-dependent effects of naloxone on discrimination learning in mice Psy-chopharmacology 73:152.Google Scholar
  5. Chipkin, R. E., Stewart, J. M., and Channabasavaiah, K., 1980, The effects of peptides on the stimulus properties of ethanol, Pharmacol. Biochem. Behav. 12:93.PubMedCrossRefGoogle Scholar
  6. de Wied, D., Bohus, B., van Ree, J. M., Kovács, G. L., and Greven, H. M., 1978a, Neuroleptic-like activity of [des-Tyr1]-γ-endorphin in rats, Lancet I:1046.CrossRefGoogle Scholar
  7. de Wied, D., Bohus, B., van Ree, J. M., and Urban, I., 1978b, Behavioral and electrophysiological effects of peptides related to lipotropin (β-LPH), J. Pharmacol. Exp. Ther. 204:570.PubMedGoogle Scholar
  8. de Wied, D., Kovács, G. L., Bohus, B., van Ree, J. M., and Greven, H. M., 1978c, Neuroleptic activity of the neuropeptide β-LPH62–77 ([des-Tyr1]-γ-endorphin; DT7E]), Eur. J. Pharmacol. 49:427.PubMedCrossRefGoogle Scholar
  9. Di Giulio, A. M., Majane, E. M., and Yang, H. Y., 1979, On the distribution of (Met 5)- and (Leu 5)-enkephalins in the brain of the rat, guinea-pig and calf, Br. J. Pharmacol. 66:297.PubMedGoogle Scholar
  10. Dingledine, R., 1981, Possible mechanisms of enkephalin action on hippocampal CAI pyramidal neurons, J. Neurosci. 1:1022.PubMedGoogle Scholar
  11. Dorsa, D. M., van Ree, J. M., and de Wied, D., 1979, Effects of [des-Tyr1]γ-endorphin and α-endorphin on substantia nigra self-stimulation, Pharmacol. Biochem. Behav. 10:899.PubMedCrossRefGoogle Scholar
  12. Esposito, R. U., Perry, W., and Kornetsky, C., 1980, Effects of d-amphetamine and naloxone on brain stimulation reward, Psychopharmacology 69:187.PubMedCrossRefGoogle Scholar
  13. Fry, J. P., Zieglgänsberger, W., and Herz, A., 1979, Specific versus nonspecific actions of opioids on hippocampal neurones in the rat brain, Brain Res. 163:295.PubMedCrossRefGoogle Scholar
  14. Gähwiler, B. H., 1980, Excitatory action of opioid peptides and opiates on cultured hippocampal pyramidal cells, Brain Res. 194:193.PubMedCrossRefGoogle Scholar
  15. Gallagher, M., and Kapp, B. S., 1978, Manipulation of opiate activity in the amygdala alters memory processes, Life Sci. 23:1973.PubMedCrossRefGoogle Scholar
  16. Gallagher, M., Kapp, B. S., McNall, C. L., and Pascoe, J. P., 1981, Opiate effects in the amygdala central nucleus on heart rate conditioning in rabbits, Pharmacol. Biochem. Behav. 14:497.PubMedCrossRefGoogle Scholar
  17. Gorelick, D. A., Catlin, D. H., George, R., and Li, C. H., 1978, Beta-endorphin is behaviorally active in rats after chronic intravenous administration, Pharmacol Biochem. Behav. 9:385.PubMedCrossRefGoogle Scholar
  18. Hernandez, L. L., and Powell, D. A., 1980, Effects of naloxone on Pavlovian conditioning of eyeblink and heart rate responses in rabbits, Life Sci. 27:863.PubMedCrossRefGoogle Scholar
  19. Hudson, R., King, A., Singer, G., Tucker, A., Coy, D. H., and Kastin, A. J., 1980, Schedule-induced self-injection of enkephalin and heroin by the rat, in: Problems in Pain (C. Peck and M. Wallace, eds.), pp. 73–77, Pergamon Press, Elmsford, N.Y.Google Scholar
  20. Izquierdo, I., 1979, Effect of naloxone and morphine on various forms of memory in the rat: Possible role of endogenous opiate mechanisms in memory consolidation, Psychopharmacology 66:199.PubMedCrossRefGoogle Scholar
  21. Izquierdo, I., 1980a, Effect of beta-endorphin and naloxone on acquisition, memory and retrieval of shuttle avoidance and habituation learning in rats, Psychopharmacology 69:115.CrossRefGoogle Scholar
  22. Izquierdo, I., 1980b, Effects of a low and a high dose of β-endorphin on acquisition and retention in the rat, Behav. Neural Biol 30:460.PubMedCrossRefGoogle Scholar
  23. Izquierdo, I., and Dias, R. D., 1981, Retrograde amnesia caused by Met-, Leu- and des-Tyr-Met-enkaphalin in the rat and its reversal by naloxone, Neurosci. Lett. 22:189.PubMedCrossRefGoogle Scholar
  24. Izquierdo, I., and Graudenz, M., 1980, Memory facilitation by naloxone is due to release of dopaminergic and beta-adrenergic systems from tonic inhibition, Psychopharmacology 67:265.PubMedCrossRefGoogle Scholar
  25. Izquierdo, I., Paiva, A. C., and Elisabetsky, E., 1980a, Post-training intraperitoneal administration of Leu-enkephalin and β-endorphin causes retrograde amnesia for two different tasks in rats, Behav. NeurabBiol. 28:246.CrossRefGoogle Scholar
  26. Izquierdo, I., Souza, D. O., Carrasco, M. A., Dias, R. D., Perry, M. L., Eisinger, S., Elisabetsky, E., and Vendite, D. A., 1980b, Beta-endorphin causes retrograde amnesia and is released from the rat brain by various forms of training and stimulation, Psychopharmacology 70:173.PubMedCrossRefGoogle Scholar
  27. Jensen, R. A., Martinez J. L., Jr., Messing, R. B., Spiehler, V. R., Vasquez, B. J., Soumireu-Mourat, B., Liang, K. C., and McGaugh, J. L., 1978, Morphine and naloxone alter memory in rats, Soc. Neurosci. Abstr. 4:260.Google Scholar
  28. Jensen, R. A., Messing, R. B., Martinez, J. L., Jr., Vasquez, B. J., and McGaugh, J. L., 1980a, Opiate modulation of learning and memory in the rat, in: Aging in the 1980’s: Psychological Issues (L. W. Poon, ed.), pp. 191–200, American Psychological Association, Washington, D.C.CrossRefGoogle Scholar
  29. Jensen, R. A., Messing, R. B., Spiehler, V. R., Martinez, J. L., Jr., Vasquez, B. J., and McGaugh, J. L., 1980b, Memory, opiate receptors, and aging, Peptides l(Suppl. 1):197.Google Scholar
  30. Kastin, A. J., Scollan, E. L., King, M. G., Schally, A., and Coy, D., 1976, Enkephalin and a potent analog facilitate maze performance after intraperitoneal administration in rats, Pharmacol. Biochem. Behav. 5:691.PubMedCrossRefGoogle Scholar
  31. Kastin, A. J., Kostrzewa, R. M., Schally, A. V., and Coy, D. H., 1980a, Neonatal administration of Met-enkephalin facilitates maze performance of adult rats, Pharmacol. Biochem. Behav. 13:883.PubMedCrossRefGoogle Scholar
  32. Kastin, A. J., Mauk, M. D., Schally, A. V., and Coy, D. H., 1980b, Unusual dose-related effect of an endorphin analog in a complex maze, Physiol. Behav. 25:959.PubMedCrossRefGoogle Scholar
  33. Katz, R. J., and Gormezano, G., 1979, A rapid and inexpensive technique for assessing the reinforcing effects of opiate drugs, Pharmacol. Biochem. Behav. 11:231.PubMedCrossRefGoogle Scholar
  34. Kiraly, I., Borsy, J., Tapfer, M., and Graf, L., 1980, Study on the neuroleptic activity of endorphins, in: Opiate Receptors and the Neurochemical Correlates of Pain (S. Furst, ed.), pp. 93–99, Pergamon Press, Elmsford, N.Y.Google Scholar
  35. Kovács, G. L., Bohus, B., and de Wied, D., 1981, Retention of passive avoidance behavior in rats following α- and γ-endorphin administration: Effects of post-learning treatments, Neurosci. Lett. 22:79.PubMedCrossRefGoogle Scholar
  36. Kuhar, M. J., Pert, C. B., and Snyder, S. H., 1973, Regional distribution of opiate receptor binding in monkey and human brain, Nature (London) 245:447.CrossRefGoogle Scholar
  37. Law, P.-Y., Loh, H. H., and Li, C. H., 1979, Properties and localization of beta-endorphin receptor in rat brain, Proc. Natl. Acad. Sci. USA 76:5455.PubMedCrossRefGoogle Scholar
  38. Le Moal, M., Koob, G. J., and Bloom, F. E., 1979, Endorphins and extinction: Differential actions on appetitive and adversive tasks, Life Sci. 24:1631.PubMedCrossRefGoogle Scholar
  39. Lindberg, L, Smythe, S. J., and Dahl, J. L., 1979, Regional distribution of enkephalin in bovine brain, Brain Res. 168:200.PubMedCrossRefGoogle Scholar
  40. Martinez, J. L., Jr., and Rigter, H., 1980, Endorphins alter acquisition and consolidation of an inhibitory avoidance response in rats, Neurosci. Lett. 19:197.PubMedCrossRefGoogle Scholar
  41. Martinez, J. L., Jr., Jensen, R. A., Craeger, R., Veliquette, J., Messing, R. B., McGaugh, J. L., and Lynch, G., 1979, Selective effects of enkephalin on electrical activity of the in vitro hip-pocampal slice, Behav. Neural Biol. 26:128.PubMedCrossRefGoogle Scholar
  42. Mello, N. K., and Mendelson, J. H., 1978, Self-administration of an enkephalin analog by rhesus monkey, Pharmacol. Biochem. Behav. 9:579.PubMedCrossRefGoogle Scholar
  43. Messing, R. B., Jensen, R. A., Martinez, J. L., Jr., Spiehler, V. R., Vasquez, B. J., Soumireu-Mourat, B., Liang, K. C., and McGaugh, J. L., 1979, Naloxone enhancement of memory, Behav. Neural Biol. 27:266.PubMedCrossRefGoogle Scholar
  44. Messing, R. B., Vasquez, B. J., Spiehler, V. R., Martinez, J. L., Jr., Jensen, R. A., Rigter, H., and McGaugh, J. L., 1980, 3H-Dihydromorphine binding in brain regions of young and aged rats, Life Sci. 26:921.PubMedCrossRefGoogle Scholar
  45. Morley, J. E., Baranetsky, N. G., Wingert, T. D., Carlson, H. E., Hershman, J. M., Melmed, S., Levin, S. R., Jamison, K. R., Weitzman, R., Chang, R. J., and Varner, A. A., 1980, Endocrine effects of naloxone-induced opiate receptor blockade, J. Clin. Endocrinol. Metab. 50:251.PubMedCrossRefGoogle Scholar
  46. Olds, M. E., and Williams, K. N., 1980, Self-administration of D-Ala2-Met-enkephalinamide at hypothalamic self-stimulation sites, Brain Res. 194:155.PubMedCrossRefGoogle Scholar
  47. Oliverio, A., and Castellano, C., 1974, Genotype-dependent sensitivity and tolerance to morphine and heroin: Dissociation between opiate-induced running and analgesia in the mouse, Psy-chopharmacologia 39:13.Google Scholar
  48. Olson, G. A., Olson, R. D., Kastin, A. J., Green, M. T., Roig-Smith, R., Hill, C. W., and Coy, D. H., 1979, Effects of an enkephalin analog on complex learning in the rhesus monkey, Pharmacol. Biochem. Behav. 11:341.PubMedCrossRefGoogle Scholar
  49. Olson, G. A., Roig-Smith, R., Mauk, M. D., LaHoste, G. J., Coy, D. H., Hill, C. W., and Olson, R. D., 1981, Differential effects of neuropeptides on short-term memory in primates, Peptides 2(Suppl. 1):131.PubMedCrossRefGoogle Scholar
  50. Olson, R. D., Kastin, A. J., Micheli, G. F., Olson, G. A., Coy, D. H., and Montalbano, D. M., 1978, Effects of endorphin and enkephalin analogs on fear habituation in goldfish, Pharmacol. Biochem. Behav. 9:111.PubMedCrossRefGoogle Scholar
  51. Rigter, H., 1978, Attenuation of amnesia in rats by systemically administered enkephalins, Science 200:83.PubMedCrossRefGoogle Scholar
  52. Rigter, H., Greven, H., and van Riezen, H., 1977, Failure of naloxone to prevent reduction of amnesia by enkephalins, Neuropharmacology 16:545.PubMedCrossRefGoogle Scholar
  53. Rigter, H., Hannan, T. J., Messing, R. B., Martinez, J. L., Jr., Vasquez, B. J., Jensen, R. A., Veliquette, J., and McGaugh, J. L., 1980a, Enkephalins interfere with acquisition of an active avoidance response, Life Sci. 26:337.PubMedCrossRefGoogle Scholar
  54. Rigter, H., Jensen, R. A., Martinez, J. L., Jr., Messing, R. B., Vasquez, B. J., Liang, K. C., and McGaugh, J. L., 1980b, Enkephalin and fear-motivated behavior, Proc. Natl. Acad. Sci. USA 77:3729.PubMedCrossRefGoogle Scholar
  55. Roemer, D., Buescher, H. H., Hill, R. C., Pless, J., Bauer, W., Cardinaux, F., Closse, A., Hauser, D., and Huquenin, R., 1977, A synthetic enkephalin analogue with prolonged parenteral and oral analgesic activity, Nature (London) 268:547.CrossRefGoogle Scholar
  56. Scoville, W. B., and Milner, B., 1957, Loss of recent memory after bilateral hippocampal lesions, J. Neurol. Neurosurg. Psychiatry 20:11.PubMedCrossRefGoogle Scholar
  57. Stapleton, J. M., Lind, M. D., Merriman, V. J., Bozarth, M. A., and Reid, L. D., 1979a, Affective consequences and subsequent effects on morphine self-administration of D-Ala2-methionine enkephalin, Physiol. Psychol. 7:146.Google Scholar
  58. Stapleton, J. M., Merriman, V. J., Coogle, C. L., Gelbard, S. D., and Reid, L. D., 1979b, Naloxone reduces pressing for intracranial stimulation of sites in the periaqueductal gray area, accumbens nucleus, substantia nigra, and lateral hypothalamus, Physiol. Psychol. 7: 427.Google Scholar
  59. Stein, L., and Belluzzi, J. D., 1979, Brain endorphins: Possible role in reward and memory formation, Fed. Proc. 38:2468.PubMedGoogle Scholar
  60. Stilwell, D. J., Levitt, R. A., Horn, C. A., Irvin, M. D., Gross, K., Parsons, K. S., Scott, R. H., and Bradley, E. L., 1980, Naloxone and shuttlebox self-stimulation in the rat, Pharmacol. Biochem. Behav. 13:739.PubMedCrossRefGoogle Scholar
  61. Taylor, D., Hoffer, B., Zieglgänsberger, W., Siggins, G., Ling, N., Seiger, A., and Ohlson, L., 1979, Opioid peptides excite pyramidal neurons and evoke epileptiform activity in hippocampal transplants in oculo, Brain Res. 176:135.PubMedCrossRefGoogle Scholar
  62. van der Kooy, D., LePiane, F. G., and Phillips, A. G., 1977, Apparent independence of opiate reinforcement and electrical self-stimulation systems in rat brain, Life Sci. 20:981.PubMedCrossRefGoogle Scholar
  63. Vasquez, B. J., Jensen, R. A., Messing, R. B., Martinez, J. L., Jr. Rigter, H., and McGaugh, J. L., 1979, Naloxone impairs memory in aged rats, Pharmacologist 21:269.Google Scholar
  64. Volavka, J., Dornbush, R., Mallya, A., and Cho, D., 1979, Naloxone fails to affect short-term memory in man, Psychiatry Res. 1:89.PubMedCrossRefGoogle Scholar
  65. Weibel, S. L., and Wolf, H. H., 1979, Opiate modification of intracranial self-stimulation in the rat, Pharmacol. Biochem. Behav. 10:71.PubMedCrossRefGoogle Scholar
  66. Zakarian, S., and Smyth, D., 1979, Distribution of active and inactive forms of endorphins in rat pituitary and brain, Proc. Natl. Acad. Sci. USA 76:5972.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1984

Authors and Affiliations

  • Gayle A. Olson
    • 1
  • Richard D. Olson
    • 1
  • Abba J. Kastin
    • 2
  • David H. Coy
    • 3
  1. 1.Department of PsychologyUniversity of New OrleansNew OrleansUSA
  2. 2.Veterans Administration Medical Center and Tulane University School of MedicineNew OrleansUSA
  3. 3.Tulane University School of MedicineNew OrleansUSA

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