Oxytocin and Behavior

  • G. L. Kovács
Part of the Current Topics in Neuroendocrinology book series (CT NEUROENDOCRI, volume 6)


The past 10 years have witnessed the growth of the view that neuropeptides are essential to the functional integrity of the central nervous system. Oxytocin (OXT), which was long considered to be implicated in milk ejection only, is a neuropeptide with potent behavioral effects. Since the original discovery by Sterba (1974), a great number of morphological (for reviews, see Buijs 1983; Swanson and Sawchenko 1983; Sofroniew 1983; Palkovits and Brownstein 1983; Kozlowski et al. 1983) and biochemical (Dogterom et al. 1978; Mens et al. 1983; Kovács et al. 1985d; Hawthorn et al. 1984) results indicate that the biologically active OXT is present in various extrahypothalamic (mainly limbic and brainstem) brain regions. The release of extrahypothalamic OXT by depolarizing stimuli has been demonstrated (Buijs and Van Heerikhuize 1982), and the existence of specific binding sites for OXT (putative OXT receptors) has been described in limbic brain structures (Ferrier et al. 1983; Brinton et al. 1984). However, the biological significance of OXT in the brain is not clear. The neuropeptide has been implicated in the regulation of behavioral reactions. Evidence has accumulated that OXT attenuates learning and memory processes (for review, see Kovács and Telegdy 1982), regulates the adaptive response to narcotic analgesics (Kovács et al. 1984 b, c), and alters the efficacy of addictive drugs (Van Ree and De Wied 1977 a; Kovács and Telegdy 1984; Kovács et al. 1985 a).


Avoidance Behavior Passive Avoidance Maternal Behavior Retrograde Amnesia Morphine Tolerance 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abood LG, Knapp R, Mitchell T, Booth H, Schwaab L (1980) Chemical requirements of vasopressin for barrel rotation convulsions and reversal by oxytocin. J Neurosci Res 5:191–199PubMedCrossRefGoogle Scholar
  2. Andén NE, Dahlström A, Fuxe K, Larsson K (1966) Functional role of the nigro-neostriatal dopamine neurons. Acta Pharmacol Toxicol 24:263–274CrossRefGoogle Scholar
  3. Andén NE, Alander T, Grabowska-Andén M, Liljeberg B, Lindgren S, Thornström U (1984) The pharmacology of pre- and postsynaptic dopamine receptors: differential effects of dopamine receptor agonists and antagonists. In: Usdin E, Carlsson A, Dahlström A, Engel J (eds) Catecholamines, part B: Neuropharmacology and central nervous system - theoretical aspects. Alan Liss, New York, pp 19–24Google Scholar
  4. Andrews JS, Newton BA, Sahgal A (1983) The effect of vasopressin on positively rewarded responding and on locomotor activity in rats. Neuropeptides 4:17–29PubMedCrossRefGoogle Scholar
  5. Barbeau A, Roy M, Kastin AJ (1976) Double-blind evaluation of oral L-prolyl-L-leucyl- glycine amide in Parkinson’s disease. Can Med Assoc J 114:120–122PubMedGoogle Scholar
  6. Bhargava HN (1983) Effect of cyclo(leu-gly) on the supersensitivity of dopamine receptors in spontaneously hypertensive rats. Life Sci 32:2131–2137PubMedCrossRefGoogle Scholar
  7. Bhargava HN (1984) Enhanced striatal 3H-spiroperidol binding induced by chronic haloperidol treatment inhibited by peptides administered during the withdrawal phase. Life Sci 34:873–879PubMedCrossRefGoogle Scholar
  8. Bhargava HN, Pandey RN, Matwyshyn GA (1983) Effects of prolyl-leucyl-glycinamide and cyclo(leucyl-glycine) on morphine-induced antinociception and brain μ, σ and κ opiate receptors. Life Sci 32:2095–2101CrossRefGoogle Scholar
  9. Bigl H, Stark H, Ott T, Sterba G, Matthies HJ (1977) Beeinflussung von Lernprozessen durch Hinterlappenhormone am Beispiel der Ratte. Sitzungsberichte der Akademie der Wissenschaften der DDR (Berlin, DDR) 5:84–90Google Scholar
  10. Björklund A, Lindvall O, Nobin A (1975) Evidence of an incerto-hypothalamic neurone system in the rat. Brain Res 89:29–42PubMedCrossRefGoogle Scholar
  11. Bohus B, Ader B, De Wied D (1972) Effects of vasopressin on active and passive avoidance behavior. Horm Behav 3:191–197PubMedCrossRefGoogle Scholar
  12. Bohus B, Kovács GL, De Wied D (1978 a) Oxytocin, vasopressin and memory: opposite effects on consolidation and retrieval processes. Brain Res 157:414–417PubMedCrossRefGoogle Scholar
  13. Bohus B, Urban I, Van Wimersma Greidanus TJB, De Wied D (1978 b) Opposite effects of oxytocin and vasopressin on avoidance behavior and hippocampal theta rhythm in the rat. Neuropharmacology 17:239–247PubMedCrossRefGoogle Scholar
  14. Bohus B, Conti L, Kovács GL, Versteeg DHG (1982) Modulation of memory processes by neuropeptides: interaction with neurotransmitter systems. In: Marsan CA, Matthies HJ (eds) Neuronal plasticity and memory formation. Raven, New York, pp 75–87Google Scholar
  15. Brinton RE, Wamsley JK, Gee KW, Wan YP, Yamamura HI (1984) (3H)Oxytocin binding sites in the rat brain demonstrated by quantitative light microscopic autoradiography. Eur J Pharmacol 102:365–367PubMedCrossRefGoogle Scholar
  16. Buijs RM (1978) Intra- and extrahypothalamic vasopressin and oxytocin pathways in the rat. Pathways to the limbic system, medulla oblongata and spinal cord. Cell Tissue Res 192:423–435PubMedCrossRefGoogle Scholar
  17. Buijs RM (1983) Vasopressin and oxytocin - their role in neurotransmission. Pharmacol Ther 22:127–141PubMedCrossRefGoogle Scholar
  18. Buijs RM, Van Heerikhuize JJ (1982) Vasopressin and oxytocin release in the brain: a synaptic event. Brain Res 252:71–76PubMedCrossRefGoogle Scholar
  19. Burbach JPH, De Wied D (1981) Memory effects and brain proteolysis of neurohypophyseal hormones. In: Schlesinger DH (ed) Neurohypophyseal peptide hormones and other biologically active peptides. Elsevier/North Holland, Amsterdam, pp 69–87Google Scholar
  20. Burbach JPH, Lebouille JLM (1983) Proteolytic conversion of arginine-vasopressin and oxytocin by brain synaptic membranes. J Biol Chem 258:1487–1494PubMedGoogle Scholar
  21. Burbach JPH, Bohus B, Kovács GL, Van Nispen JW, Greven HM, De Wied D (1983 a) Oxytocin is a precursor of potent behaviourally active neuropeptides. Eur J Pharmacol 94:125–131PubMedCrossRefGoogle Scholar
  22. Burbach JPH, Kovács GL, Wang XC, De Wied D (1983 b) Metabolites of arginine-vaso- pressin and oxytocin are highly potent neuropeptides in the brain. In: Koch G, Richter D (eds) Biochemical and clinical aspects of neuropeptides: synthesis, processing and gene structure. Academic, Orlando, pp 211–222Google Scholar
  23. Caldwell JD, Pedersen CA, Prange AJ (1984) Oxytocin facilitates sexual behavior in estrogen-treated ovariectomized rats. J Steroid Biochem 20:1510CrossRefGoogle Scholar
  24. Celis ME, Taleisnik S, Walter R (1971) Regulation of formation and proposed structure of the factor inhibiting the release of melanocyte-stimulating hormone. Proc Natl Acad Sci (USA) 68:1428–1433CrossRefGoogle Scholar
  25. Chard T, Hudson CN, Edwards CRW, Boyd NRH (1971) Release of oxytocin and vasopressin by the human fetus during labour. Nature 234:352–354PubMedCrossRefGoogle Scholar
  26. Cohn ML, Cohn M (1975) Barrel rotation induced by somatostatin in the non-lesioned rat. Brain Res 96:138–141PubMedCrossRefGoogle Scholar
  27. Contreras P, Takemori AE (1981) Facilitation of morphine-induced tolerance and physical dependence by prolyl-leucyl-glycinamide. Eur J Pharmacol 71:259–268PubMedCrossRefGoogle Scholar
  28. Cools AR, Broekkamp CLE, Gieles LCM, Megens A, Mortieaux HJGM (1977) Site of action of development of partial tolerance to morphine in cats. Psychoneuroendocrinology 2:17–33PubMedCrossRefGoogle Scholar
  29. Costall B, Domeney AM, Naylor RJ (1984) Long-term consequences of antagonism by neuroleptics of behavioural events occurring during mesolimbic dopamine infusion. Neuropharmacology 23:287–294PubMedCrossRefGoogle Scholar
  30. De Kloet ER, Rotteveel F, Voorhuis TD, Terlou M (1985) Topography of binding sites for neurohypophyseal hormones in rat brain. Eur J Pharmacol 110:113–119PubMedCrossRefGoogle Scholar
  31. Delanoy RL, Dunn AJ, Tintner R (1978) Behavioral responses to intracerebroventricularly administered neurohypophyseal peptides in mice. Horm Behav 11:348–362PubMedCrossRefGoogle Scholar
  32. Destrade C, Jafford R (1978) Post-trial hippocampal and lateral hypothalamic electrical stimulation. Facilitation of long-term memory of appetititive and avoidance learning tasks. Behav Biol 22:354–374PubMedCrossRefGoogle Scholar
  33. De Wied D (1965) The influence of posterior and intermediate lobe of the pituitary and pituitary peptides on the maintenance of conditioned avoidance response in rats. Int J Neuropharmacol 4:157–167CrossRefGoogle Scholar
  34. De Wied D (1969) Effects of peptide hormones on behavior. In: Ganong W, Martini L (eds) Frontiers in neuroendocrinology. Oxford University Press, New York, pp 97–140Google Scholar
  35. De Wied D (1976) Behavioral effects of intraventricularly administered vasopressin and vasopressin fragments. Life Sci 19:685–690PubMedCrossRefGoogle Scholar
  36. De Wied D (1979) Pituitary neuropeptides and behavior. In: Fuxe K, Hökfelt T, Luft R (eds) Central regulation of the endocrine system. Plenum, New York, pp 297–314Google Scholar
  37. De Wied D, Bohus B (1966) Long term and short term effect on retention of a conditioned avoidance response in rats by treatment respectively with long acting pitressin or α- MSH. Nature 212:1484–1486PubMedCrossRefGoogle Scholar
  38. De Wied D, Bohus B (1979) Modulation of memory processes by neuropeptides of hypothalamic-neurohypophyseal origin. In: Brazier MAB (ed) Brain mechanisms in memory and learning: from the single neuron to man. Raven, New York, pp 139–149Google Scholar
  39. De Wied D, Gispen WH (1976) Impaired development of tolerance to morphine analgesia in rats with hereditary diabetes insipidus. Psychopharmacology 46:27–29CrossRefGoogle Scholar
  40. De Wied D, Gispen WH (1977) Behavioral effects of peptides. In: Gainer H (ed) Peptides in neurobiology. Plenum, New York, pp 397–448Google Scholar
  41. De Wied D, Versteeg DHG (1979) Neurohypophyseal principles and memory. Fed Proc 38:2348–2354PubMedGoogle Scholar
  42. De Wied D, Van Wimersma Greidanus TJB, Bohus B, Urban I, Gispen WH (1976) Vasopressin and memory consolidation. In: Corner MA, Swaab DF (eds) Perspectives in brain research. Prog Brain Res 45:181–191CrossRefGoogle Scholar
  43. De Wied D, Gaffori O, Van Ree JM, De Jong W (1984) Central target for the behavioural effects of vasopressin neuropeptides. Nature 308:276–278PubMedCrossRefGoogle Scholar
  44. Dickinson SL, Slater P (1980) Opiate receptor antagonism by L-prolyl-L-leucyl-glycinam- ide, MIF-I. Peptides 1:293–299PubMedCrossRefGoogle Scholar
  45. Dogterom J, Snijdewindt FGM, Buijs RM (1978) The distribution of vasopressin and oxytocin in the rat brain. Neurosci Lett 9:341–346PubMedCrossRefGoogle Scholar
  46. Drago F, Bohus B, De Wied D (1981) Interaction between vasopressin and oxytocin in the modulation of passive avoidance retention of the rat. Neurosci Lett [Suppl] 7:S260Google Scholar
  47. Drago F, Kovács GL, Scapagnini U (1984) Prolactin-induced behavioral effects and opioids. In: Delitalia G, Motta M, Serio M (eds) Opioid modulation of endocrine function. Frontiers in neuroscience. Raven, New York, pp 137–145Google Scholar
  48. Drago F, Kovács GL, Szabó G, Scapagnini U, Telegdy G (1985) Effects of haloperidol on morphine-induced analgesia, morphine tolerance and withdrawal in hyperprolactinaemic rats. Neuropharmacology 24:1027–1031PubMedCrossRefGoogle Scholar
  49. Ehrensing RH, Kastin AJ, Larsons PF, Bishop GA (1978) Melanocyte-stimulating-hor- mone-release-inhibiting factor-I and tardive dyskinesia. Dis Nerv Syst 38:303–307Google Scholar
  50. Esposito R, Kornetsky C (1977) Morphine lowering of self-stimulation thresholds: lack of tolerance with long-term administration. Science 195:189–191PubMedCrossRefGoogle Scholar
  51. Essmann WB (1971) The role of biogenic amines in memory consolidation. In: Adám G (ed) Biology of memory. Akadémiai Kiadó/Plenum, Budapest, pp 213–238Google Scholar
  52. Ettenberg A, Van der Koy D, Le Moal M, Koob GF, Bloom FE (1983) Can aversive properties of (peripherally-injected) vasopressin account for its putative role in memory? Behav Brain Res 7:331–350PubMedCrossRefGoogle Scholar
  53. Fahrbach SE, Morrell JI, Pfaff DW (1985) Role of oxytocin in the onset of estrogen-facilitated maternal behavior. In: Amico JA, Robinson AG (eds) Oxytocin: clinical and laboratory aspects. Elsevier, Amsterdam, pp 372–388Google Scholar
  54. Fehm-Wolsdorf G, Born J, Voigt KH, Fehm HL (1984) Human memory and neurohypophyseal hormones: opposite effects of vasopressin and oxytocin. Psychoneuroendocrinology 9:285–292CrossRefGoogle Scholar
  55. Ferrier BM, Kennett DJ, Devlin MC (1980) Influence of oxytocin on human memory processes. Life Sci 27:2311–2317PubMedCrossRefGoogle Scholar
  56. Ferrier BM, McClorry SA, Cochrane AW (1983) Specific binding of (3H)oxytocin in female rat brain. Can J Physiol Pharmacol 61:989–995PubMedCrossRefGoogle Scholar
  57. Feuerstein G, Zerbe RL, Faden I (1984) Central cardiovascular effects of vasotocin, oxytocin and vasopressin in conscious rats. J Pharmacol Exp Ther 228:348–353PubMedGoogle Scholar
  58. Folley SJ, Knaggs GS (1966) Milk-ejection activity (oxytocin) in the external jugular vein blood of the cow, goat and sow, in relation to the stimulus of licking and suckling. J Endocrinol 34:197–214PubMedCrossRefGoogle Scholar
  59. Friedman E, Friedman J, Gershon S (1973) Dopamine synthesis: stimulation by a hypothalamic factor. Science 182:831–832PubMedCrossRefGoogle Scholar
  60. Fuxe K, Hökfelt T, Ungerstedt U (1968) Localization of indolalkylamines in the CNS. In: Garattini S, Shore PE (eds) Advances in pharmacology, vol 6, part A, Academic, New York, pp 235–251Google Scholar
  61. Gash DM, Thomas GJ (1983) What is the importance of vasopressin in memory processes? Trends Neurosci 60:197–198CrossRefGoogle Scholar
  62. Gibbs DM (1984) Dissociation of oxytocin, vasopressin and corticotropin secretion during different types of stress. Life Sci 35:487–491PubMedCrossRefGoogle Scholar
  63. Hagan JJ, Bohus B (1984) Vasopressin prolongs bradycardiac response during orientation. Behav Neural Biol 41:77–83PubMedCrossRefGoogle Scholar
  64. Hawthorn J, Ang VTY, Jenkins JS (1984) Comparison of the distribution of oxytocin and vasopressin in the rat brain. Brain Res 307:289–294PubMedCrossRefGoogle Scholar
  65. Himmelsbach CK (1943) With reference to physical dependence. Fed Proc 2:201–203Google Scholar
  66. Hoffmann PL, Ritzmann RF, Walter R, Tabakoff B (1978) Arginine vasopressin maintains ethanol tolerance. Nature 276:614–616CrossRefGoogle Scholar
  67. Izquierdo I, Perry ML, Dias RD, Souza DO, Elisabetsky E, Carrasco MA, Orsingher OA, Netto CA (1981) Endogenous opioids, memory modulation, and state dependency. In: Martinez JL, Jensen RA, Messing RB, Rigter H, McGaugh JL (eds) Endogenous peptides and learning and memory processes. Academic, New York, pp 269–290Google Scholar
  68. Joëls M, Urban IJA (1982) The effect of microiontophoretically applied vasopressin and oxytocin on single neurones in the septum and dorsal hippocampus of the rat. Neurosci Lett 33:79–84PubMedCrossRefGoogle Scholar
  69. Judge MA, Quartermain D (1982) Characteristics of retrograde amnesia following reactivation of memory in mice. Physiol Behav 28:585–590PubMedCrossRefGoogle Scholar
  70. Kastin AJ, Plotnikoff NP, Sandman CA, Spirtes MA, Kostrzewa RM, Paul SM, Stratton LO, Miller LH, Labrie F, Schally AV, Goldman H (1975) The effects of MSH and MIF on the brain. In: Stumpf WE, Grant LD (eds) Anatomical neuroendocrinology. Karger, Basel, pp 290–297Google Scholar
  71. Kastin AJ, Nissen C, Zadina JE, Schally AV, Ehrensing RH (1980) Naloxone-like actions of MIF-1 do not require the presence of the pituitary. Pharmacol Biochem Behav 13:907–912PubMedCrossRefGoogle Scholar
  72. Kastin AJ, Zadina JE, Banks WA, Graf MV (1984) Misleading concepts in the field of brain peptides. Peptides 5:249–253PubMedCrossRefGoogle Scholar
  73. Kennett DJ, Devlin MC, Ferrier BM (1982) Influence of oxytocin on human memory processes: validation by a control study. Life Sci 31:273–275PubMedCrossRefGoogle Scholar
  74. Koob GF, Le Moal M, Gaffori O, Manning M, Sawyer WH, Rivier J, Bloom FE (1981) Arginine vasopressin and a vasopressin antagonist peptide: opposite effects on extinction of active avoidance in rats. Regul Peptides 2:153–163CrossRefGoogle Scholar
  75. Kordower JH, Bodnar RJ (1984) Vasopressin analgesia: specificity of action and nonopioid effects. Peptides 5:747–756PubMedCrossRefGoogle Scholar
  76. Kovács GL, De Wied D (1981) Endorphin influences on learning and memory. In: Martinez JL, Jensen RA, Messing RB, Rigter H, McGaugh JL (eds) Endogenous peptides and learning and memory processes. Academic, New York, pp 231–247Google Scholar
  77. Kovács GL, De Wied D (1983) Hormonally active arginine-vasopressin suppresses endotoxin-induced fever in rats: lack of effect of oxytocin and a behaviorally active vasopressin fragment. Neuroendocrinology 37:258–261PubMedCrossRefGoogle Scholar
  78. Kovács GL, Telegdy G (1978) Indoleamines and behavior. The possible role of serotoni- nergic mechanisms in the pituitary-adrenocortical hormone-induced behavioral actions. In: Lissák K (ed) Recent progress of neurobiology in Hungary, vol 7. Akadémiai Kiadó, Budapest, pp 31–97Google Scholar
  79. Kovács GL, Telegdy G (1982) Role of oxytocin in memory and amnesia. Pharmacol Ther 18:375–395PubMedCrossRefGoogle Scholar
  80. Kovács GL, Telegdy G (1983) Effects of oxytocin, des-glycinamide-oxytocin and anti-oxytocin serum on the α-MPT-induced disappearance of catecholamines in the rat brain. Brain Res 268:307–314PubMedCrossRefGoogle Scholar
  81. Kovács GL, Telegdy G (1984) Oxytocin diminishes narcotic addiction: effects on morphine tolerance/withdrawal and heroin self-administration. Neurosci Lett [Suppl] 18:S354Google Scholar
  82. Kovács GL, Telegdy G (1985) Oxytocin in memory and reinforcement. In: Amico J, Robinson AG (eds) Oxytocin: clinical and laboratory studies. Elsevier, Amsterdam, pp 359–371Google Scholar
  83. Kovács GL, Vécsei L, Sazbó G, Telegdy G (1977) The involvement of catecholaminergic mechanisms in the behavioural action of vasopressin. Neurosci Lett 5:337–344PubMedCrossRefGoogle Scholar
  84. Kovács GL, Vécsei L, Telegdy G (1978) Opposite action of oxytocin to vasopressin in passive avoidance behavior in rats. Physiol Behav 20:801–802PubMedCrossRefGoogle Scholar
  85. Kovács GL, Bohus B, Versteeg DHG, De Kloet ER, De Wied D (1979) Effect of oxytocin and vasopressin on memory consolidation: sites of action and catecholaminergic correlates after local microinjection into limbic-midbrain structures. Brain Res 175:303–314PubMedCrossRefGoogle Scholar
  86. Kovács GL, Bohus B, Versteeg DHG (1980) The interaction of posterior pituitary neuropeptides with monoaminergic neurotransmission: significance in learning and memory processes. Prog Brain Res 53:123–140PubMedCrossRefGoogle Scholar
  87. Kovács GL, Szontágh L, Baláspiri L, Hódi K, Bohus P, Telegdy G (1981) On the mode of action of an oxytocin derivative (Z-Pro-D-Leu) on morphine dependence in mice. Neuropharmacology 20:647–651PubMedCrossRefGoogle Scholar
  88. Kovács GL, Bohus B, Versteeg DHG, Telegdy G, De Wied D (1982 a) Neurohypophyseal hormones and memory. In: Yoshida H, Hagihara Y, Ebashi S (eds) Advances in pharmacology and therapeutics II, vol 1. CNS pharmacology. Neuropeptides, Pergamon, Oxford, pp 175–187Google Scholar
  89. Kovács GL, Buijs RM, Bohus B, Van Wimersma Greidanus TJB (1982 b) Microinjection of arginine8-vasopressin antiserum into the dorsal hippocampus attenuates passive avoidance behavior in rats. Physiol Behav 28:45–48PubMedCrossRefGoogle Scholar
  90. Kovács GL, Ribárszki Z, Telegdy G (1983 a) Reversal of electroconvulsive shock-induced amnesia by neuropeptides. In: Endröczi E, De Wied D, Angelucci L, Scapagnini U (eds) Neuropeptides and psychosomatic processes. Akadémiai Kiadó, Budapest, pp 167–174Google Scholar
  91. Kovács GL, Acsai L, Tihanyi A, Faludi M, Telegdy G (1983 b) Influence of Z-prolyl-D- leucine on α-MPT-induced catecholamine utilization in specific mouse brain nuclei. Pharmacol Biochem Behav 18:345–349PubMedCrossRefGoogle Scholar
  92. Kovács GL, Acsai L, Tihanyi A, Telegdy G (1983 c) Catecholamine utilization in distinct mouse brain nuclei during acute morphine treatment, morphine tolerance and withdrawal syndrome. Eur J Pharmacol 93:149–158PubMedCrossRefGoogle Scholar
  93. Kovács GL, Izbáki F, Horváth Z, Telegdy G (1984 a) Effects of oxytocin and a derivative (Z-prolyl-D-leucine) on morphine tolerance/dependence are mediated by the limbic system. Behav Brain Res 14:1–8PubMedCrossRefGoogle Scholar
  94. Kovács GL, Schwarzberg H, Veldhuis HD, Telegdy G (1984 b) Influences of oxytocin on behavioral processes: role of monoaminergic neurotransmission. Acta Physiol Hung 63:249Google Scholar
  95. Kovács GL, Horváth Z, Falkay G (1984 c) Brain dopamine and neuropeptide interactions in narcotic addiction: I. The role of pre- and postsynaptic receptors. Annual meeting of the Hungarian physiological society, Szeged, July 5–7, 1984, p 55Google Scholar
  96. Kovács GL, Telegdy G, Hódi K (1984d) Drugs affecting brain dopamine interfere with the effect of Z-prolyl-D-leucine on morphine withdrawal. Pharmacol Biochem Behav 21:345–348PubMedCrossRefGoogle Scholar
  97. Kovács GL, Borthaiser Z, Telegdy G (1985 a) Oxytocin reduces heroin self-administration in heroin-tolerant rats. Life Sci 37:17–26PubMedCrossRefGoogle Scholar
  98. Kovács GL, Horváth Z, Sarnyai Z, Faludi M, Telegdy G (1985 b) Oxytocin and a C-terminal derivative (Z-prolyl-D-leucine) attenuate tolerance to and dependence on morphine and interact with dopaminergic neurotransmission in the mouse brain. Neuropharmacology 24:413–419PubMedCrossRefGoogle Scholar
  99. Kovács GL, Telegdy G, Laczi F, László F (1985 c) Oxytocin and vasopressin in memory and amnesia. In: Will BE, Schmitt P, Dalrymple-Alford JC (eds) Brain plasticity, learning, and memory. Plenum, New York, pp 297–301Google Scholar
  100. Kovács GL, Vecsernyés M, Laczi F, Faludi M, Telegdy G, László FA (1985 d) Acute morphine treatment and morphine tolerance/dependence alter immunoreactive oxytocin levels in the mouse hippocampus. Brain Res 328:158–160PubMedCrossRefGoogle Scholar
  101. Kozlowski GP, Nilaver G, Zimmermann EA (1983) Distribution of neurohypophyseal hormones in the brain. Pharmacol Ther 21:325–349PubMedCrossRefGoogle Scholar
  102. Krivoy WA, Zimmermann E, Lande S (1974) Facilitation of development of resistance to morphine analgesia by desglycinamide9-lysine vasopressin. Proc Natl Acad Sci (USA) 71:1852–1856CrossRefGoogle Scholar
  103. Kruse H, Van Wimersma Greidanus TJB, De Wied D (1977) Barrel rotation by vasopressin and related peptides in rats. Pharmacol Biochem Behav 7:311–313PubMedCrossRefGoogle Scholar
  104. Landfield PW, McGaugh JL (1972) Effects of electroconvulsive shock and brain stimulation on EEG cortical theta rhythms in rats. Behav Biol 7:271–278PubMedCrossRefGoogle Scholar
  105. Landfield PW, McGaugh JL, Tusa RJ (1972) Theta rhythm: a temporal correlate of memory storage processes in the rat. Science 175:87–89PubMedCrossRefGoogle Scholar
  106. Lee JM, Ritzmann RF, Fields JZ (1984) Cyclo(leu-gly) has opposite effects on D-2 dopamine receptors in different brain areas. Peptides 5:7–10PubMedCrossRefGoogle Scholar
  107. Le Douarin C, Fage D, Scatton B (1984) Effects of cyclo(leu-gly) on neurochemical indices of striatal dopaminergic supersensitivity induced by prolonged haloperidol treatment. Life Sci 34:393–399PubMedCrossRefGoogle Scholar
  108. Le Piane FG, Phillips AG (1978) Differential effects of electrical stimulation of the amygdala, caudate-putamen or substantia nigra pars compacta on taste aversion and passive avoidance in rats. Physiol Behav 21:979–985CrossRefGoogle Scholar
  109. Maroli AN, Tsang WK, Stutz RM (1978) Morphine and self-stimulation: evidence for action on a common neural substrate. Pharmacol Biochem Behav 8:119–123PubMedCrossRefGoogle Scholar
  110. McGaugh JL (1966) Time-dependent processes in memory storage. Science 153:1351–1358PubMedCrossRefGoogle Scholar
  111. McGaugh JL (1973) Drug facilitation of learning and memory. Ann Rev Pharmacol 13:229–241PubMedCrossRefGoogle Scholar
  112. McGaugh JL, Dawson RG (1971) Modification of memory storage processes. In: Honig WK, James PHR (eds) Animal memory. Academic, New York, pp 215–242Google Scholar
  113. McGaugh JL, Gold PE, Handwerker MJ, Jensen RA, Martinez JL, Meligeni JA, Vasquez BJ (1979) Altering memory by electrical and chemical stimulation of the brain. In: Brazier MAB (ed) Brain mechanisms in memory and learning: from single neuron to man. IBRO Monograph Series, vol 4. Raven, New York, pp 151–164Google Scholar
  114. Meisenberg G (1981) Short-term behavioral effects of posterior pituitary peptides in mice. Peptides 2:1–8PubMedCrossRefGoogle Scholar
  115. Meisenberg G (1982) Short-term behavioural effects of neurohypophyseal hormones: pharmacological characteristics. Neuropharmacology 21:309–316PubMedCrossRefGoogle Scholar
  116. Meisenberg G, Simmons WH (1982) Behavioral effects of intracerebroventricularly administered neurohypophyseal hormone analogs in mice. Pharmacol Biochem Behav 16:819–825PubMedCrossRefGoogle Scholar
  117. Meisenberg G, Simmons WH (1984 a) Amastatin potentiates the behavioral effects of vasopressin and oxytocin in mice. Peptides 5:535–539PubMedCrossRefGoogle Scholar
  118. Meisenberg G, Simmons WH (1984 b) Factors involved in the inactivation of vasopressin after intracerebroventricular injection in mice. Life Sci 34:1231–1240PubMedCrossRefGoogle Scholar
  119. Mens WBJ, Van Egmond MA, De Rotte AA, Van Wimersma Greidanus TJB (1982) Neurohypophyseal peptide levels in CSF and plasma during passive avoidance behavior in rats. Horm Behav 16:371–382PubMedCrossRefGoogle Scholar
  120. Mens WBJ, Witter A, Van Wimersma Greidanus TJB (1983) Penetration of neurohypophyseal hormones from plasma into cerebrospinal fluid (CSF): half-times of disappearance of these peptides from CSF. Brain Res 262:143–149PubMedCrossRefGoogle Scholar
  121. Moos F, Richard P (1983) Serotonergic control of oxytocin release during suckling in the rat: opposite effects in conscious and anesthetized rats. Neuroendocrinology 36:300–306PubMedCrossRefGoogle Scholar
  122. Nair RMG, Kastin AJ, Schally AV (1971) Isolation and structure of hypothalamic MSH release-inhibiting hormone. Biochem Biophys Res Commun 43:1376–1381PubMedCrossRefGoogle Scholar
  123. Obrist P, Webb RA, Sutterer JR, Howard JL (1970) The cardiac-somatic relationship: some reformulations. Psychophysiology 6:569–587PubMedCrossRefGoogle Scholar
  124. Palkovits M, Browstein M (1983) Extrahypothalamic distribution and action of hypothalamic hormones. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psycho-pharmacology, vol 16, Neuropeptides, Plenum, New York, pp 467–487CrossRefGoogle Scholar
  125. Pedersen CA, Prange AJ (1979) Induction of maternal behavior in virgin rats after intrace- rebroventricular administration of oxytocin. Proc Natl Acad Sci (USA) 76:6661–6665CrossRefGoogle Scholar
  126. Pedersen CA, Ascher JA, Monroe YL, Prange AJ (1982) Oxytocin induces maternal behavior in virgin female rats. Science 216:648–650PubMedCrossRefGoogle Scholar
  127. Pedersen CA, Caldwell JD, Prange AJ (1984) Oxytocin antiserum inhibits the onset of ovarian steroid-induced maternal behavior. Symposium on Oxytocin, Lac Beauport, CanadaGoogle Scholar
  128. Porsolt RD, Bertin A, Jalfre M (1977) Behavioural despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 229:327–336PubMedGoogle Scholar
  129. Quartermain D, Freedman LS, Botwinick CY, Gutwein BM (1977) Reversal of cyclohex- imide-induced amnesia by adrenergic receptor stimulation. Pharmacol Biochem Behav 7:259–267PubMedCrossRefGoogle Scholar
  130. Reppert SM, Perlow MJ, Artman HG, Ungerleider LG; Fisher DA, Klein DC (1984) The circadian rhythm of oxytocin in primate cerebrospinal fluid: effects of destruction of the suprachiasmatic nuclei. Brain Res 307:384–387PubMedCrossRefGoogle Scholar
  131. Rigter H, Van Riezen H (1978) Hormones and memory. In: Lipton MA, De Mascio A, Killam AF (eds) Psychopharmacology: a generation of progress. Raven, New York, pp 677–689Google Scholar
  132. Rigter H, Van Riezen H, De Wied D (1974) The effects of ACTH- and vasopressin-ana- logues on CO2-induced retrograde amnesia in rats. Physiol Behav 13:381–388PubMedCrossRefGoogle Scholar
  133. Rigter H, Rijk H, Crabbe JC (1980) Tolerance to ethanol and the severity of withdrawal in mice are enhanced by a vasopressin fragment. Eur J Pharmacol 64:53–68PubMedCrossRefGoogle Scholar
  134. Ritzmann RF, Walter R, Bhargava HN, Krivoy W (1980) The inhibition of the development of tolerance to and dependence on morphine by peptides. In: Ajmone Marsan C, Traczyk WZ (eds) Neuropeptides and neural transmission. Raven, New York, pp 237–244Google Scholar
  135. Ritzmann RF, Colbern DL, Zimmermann EG, Krivoy W (1984) Neurohypophyseal hormones in tolerance and physical dependence. Pharmacol Ther 23:281–312CrossRefGoogle Scholar
  136. Robinson AG, Zimmermann EA (1973) Cerebrospinal fluid and ependymal neurophysin. J Clin Invest 52:1260–1267PubMedCrossRefGoogle Scholar
  137. Robinson ICAF, Jones PM (1982) Neurohypophyseal peptides in cerebrospinal fluid: recent studies. In: Baertschi AJ, Dreifuss JJ (eds) Neuroendocrinology of vasopressin, corticoliberin and opiomelanocortins. Academic, London, pp 21–31Google Scholar
  138. Rubin BS, Menniti FS, Bridges RS (1983) Intracerebroventricular administration of oxytocin and maternal behavior in rats after prolonged and acute steroid pretreatment. Horm Behav 17:45–53PubMedCrossRefGoogle Scholar
  139. Sahgal A, Wright C (1984) Choice, as opposed to latency, measures in avoidance suggest that vasopressin and oxytocin do not affect memory in rats. Neurosci Lett 48:299–304PubMedCrossRefGoogle Scholar
  140. Sahgal A, Keith AB, Wright C, Edwardson JA (1982) Failure of vasopressin to enhance memory in a passive avoidance task in rats. Neurosci Lett 28:87–92PubMedCrossRefGoogle Scholar
  141. Sara SJ, Barnett J, Toussaint P (1982) Vasopressin accelerates appetitive discrimination learning and impairs its reversal. Behav Proc 7:157–167CrossRefGoogle Scholar
  142. Schmidt WK, Holaday JW, Loh HH, Way EL (1978) Failure of vasopressin and oxytocin to antagonize acute morphine antinociception or facilitate narcotic tolerance development. Life Sci 23:151–158PubMedCrossRefGoogle Scholar
  143. Schulz H, Kovács GL, Telegdy G (1974) Effect of physiological doses of vasopressin and oxytocin on avoidance and exploratory behaviour in rats. Acta Physiol Hung 45:211–215Google Scholar
  144. Schulz H, Kovács GL, Telegdy G (1976) The effect of vasopressin and oxytocin on avoidance behavior in rats. In: Endröczi E (ed) Cellular and molecular bases of neuroendocrine processes. Akadémiai Kiadó, Budapest, pp 555–564Google Scholar
  145. Schulz H, Kovács GL, Telegdy G (1979) Action of posterior pituitary neuropeptides on the nigro-striatal dopaminergic system. Eur J Pharmacol 57:185–190PubMedCrossRefGoogle Scholar
  146. Schwarzberg H, Unger H (1970) Änderung der Reaktionszeit von Ratten nach Applikation von Vasopressin, Oxytocin und Na-thioglykolat. Acta Biol Med Germ 24:507–516PubMedGoogle Scholar
  147. Schwarzberg H, Hartmann G, Kovács GL, Telegdy G (1976) The effect of intraventricular administration of oxytocin and vasopressin on self-stimulation in rats. Acta Physiol Hung 47:127–131Google Scholar
  148. Schwarzberg H, Betschen K, Unger H, Schulz H (1978) Beeinflussung der hypothalami- schen Selbststimulation durch intrazerebroventriculär verabreichtes Vasopressin und Oxytocin. Acta Biol Med Germ 37:1295–1296PubMedGoogle Scholar
  149. Schwarzberg H, Kovács GL, Szabô G, Telegdy G (1981) Intraventricular administration of vasopressin and oxytocin affects the steady-state levels of serotonin, dopamine and norepinephrine in rat brain. Endocrinol Exp (Bratisl) 15:75–80Google Scholar
  150. Schwarzberg H, Kovács GL, Telegdy G (1984) The influence of oxytocin on the steady-state level and accumulation of serotonin in rat brain regions. Neuropeptides 4:145–156PubMedCrossRefGoogle Scholar
  151. Siegel S (1975) Evidence from rats that morphine tolerance is a learned response. J Comp Physiol Psychol 89:498–506PubMedCrossRefGoogle Scholar
  152. Siegel S (1976) Morphine analgesic tolerance: its situation specificity supports a Pavlovian conditioning model. Science 193:323–325PubMedCrossRefGoogle Scholar
  153. Siegel S (1978) Tolerance to the hypothermic effect of morphine in the rat is a learned response. J Comp Physiol Psychol 92:1137–1149PubMedCrossRefGoogle Scholar
  154. Silverman AJ, Oldenfield BJ (1984) Synaptic input to vasopressin neurons of the paraventricular nucleus (PVN). Peptides 5:139–150PubMedCrossRefGoogle Scholar
  155. Singhal RL, Rastogi RB (1982) MIF-1: effects on norepinephrine, dopamine and serotonin metabolism in certain discrete brain regions. Pharmacol Biochem Behav 16:229–233PubMedCrossRefGoogle Scholar
  156. Sladek JR, Fields J, Phelps CJ, Khachaturian H (1984) Development of the catecholamine innervation of the supraoptic nucleus in the Brattleboro rat. Peptides 5 [Suppl 1]:151–155PubMedCrossRefGoogle Scholar
  157. Sofroniew MV (1983) Vasopressin and oxytocin in the mammalian brain and spinal cord. Trends Neurosci 6:467–472CrossRefGoogle Scholar
  158. Sterba G (1974) Ascending neurosecretory pathways of the peptidergic type. In: Knowles F, Vollrath L (eds) Neurosecretion - the final neurosecretory pathway. Springer, Berlin Heidelberg New York, pp 38–47Google Scholar
  159. Sterba G, Naumann W, Hoheisel G (1980) Exohypothalamic axons of the classical neurosecretory system and their synapses. In: McConnell PS, Boer GJ, Romijn HJ, Van de Poll NE, Corner MA (eds) Adaptive capabilities of the nervous system. Prog Brain Res 53:141–158Google Scholar
  160. Strupp B, Weingartner H, Goodwin FK, Gold PW (1984) Neurohypophyseal hormones and cognition. Pharmacol Ther 23:267–279CrossRefGoogle Scholar
  161. Swanson HH, Bolwerk E (1984) Does oxytocin play a role in the onset of maternal behaviour? J Steroid Biochem 20:1510CrossRefGoogle Scholar
  162. Swanson LW, Sawchenko PE (1983) Hypothalamic integration: organization of the paraventricular and supraoptic nuclei. Ann Rev Neurosci 6:269–324PubMedCrossRefGoogle Scholar
  163. Szabó G, Kovács GL, Baláspiri L, Telegdy G (1981) Dose-related effect of the oxytocin fragment prolyl-leucyl-glycinamide on α-MPT-induced catecholamine disappearance and serotonin levels in rat brain. Neurochem Int 3:411–416PubMedCrossRefGoogle Scholar
  164. Szabó G, Kovács GL, Telegdy G (1983) The effect of oxytocin and an oxytocin fragment (prolyl-leucyl-glycinamide) on the development of ethanol tolerance. Acta Endocrinol 103 [Suppl 256]:242Google Scholar
  165. Szabó G, Kovács GL, Telegdy G (1984) The effect of oxytocin and two of its fragments on ethanol tolerance in mice. J Steroid Biochem 20:1512CrossRefGoogle Scholar
  166. Szabó G, Kovács GL, Székeli S, Baláspiri L, Telegdy G (1985) C-terminal fragments of oxytocin (prolyl-leucyl-glycinamide and Z-prolyl-D-leucine) attenuate the development of tolerance to ethanol. Acta Physiol Hung (in press)Google Scholar
  167. Székely JI, Miglécz E, Dunai-Kovács Z, Tarnawa I, Rónai AZ, Gráf L, Bajusz S (1979) Attenuation of morphine tolerance and dependence by α-melanocyte-stimulating hormone (α-MSH). Life Sci 24:1931–1938PubMedCrossRefGoogle Scholar
  168. Tabakoff B, Ritzmann RF (1977) The effect of 6-hydroxydopamine on tolerance to and dependence on ethanol. J Pharmacol Exp Ther 203:319–321PubMedGoogle Scholar
  169. Tanaka M, Versteeg DHG, De Wied D (1977) Regional effects of vasopressin on rat brain catecholamine metabolism. Neurosci Lett 4:321–325PubMedCrossRefGoogle Scholar
  170. Telegdy G, Kovács GL (1979 a) Role of monoamines in mediating the action of hormones on learning and memory. In: Brazier MAB (ed) Brain mechanisms in memory and learning: from single neuron to man. IBRO Monograph Series, vol 4. Raven, New York, pp 249–268Google Scholar
  171. Telegdy G, Kovács GL (1979 b) Role of monoamines in mediating the action of ACTH; vasopressin and oxytocin. In: Collu R, Barbeau A, Ducharme JR, Rochefort JG (eds) Central nervous system effects of hypothalamic hormones and other peptides. Raven, New York, pp 189–205Google Scholar
  172. Thompson T, Pickens R (1975) An experimental analysis of behavioral factors in drug dependence. Fed Proc 34:1759–1770PubMedGoogle Scholar
  173. Tindal JS (1974) Stimuli that cause the release of oxytocin. In: Knobil E, Sawyer WH (eds) The pituitary gland and its neuroendocrine control, part 1. American Physiological Society, Washington, pp 257–267 (Handbook of physiology, vol 4, sect 7: Endocrinology)Google Scholar
  174. Unger H (1977) Funktionelle Aspekte der Informationsübermittelung durch die Oligopeptide Vasopressin und Oxytocin bei Säugetieren. Sitzungsberichte der Akademie der Wissenschaften der DDR, Berlin, DDR, 5:62–83Google Scholar
  175. Ungerstedt U, Ljungberg T, Schultz W (1978) Dopamine receptor mechanisms: behavioral and electrophysiological studies. In: Roberts JL, Woodruff GN, Iversen LL (eds) Advances in biochemical pharmacology, vol 19. Raven, New York, pp 311–321Google Scholar
  176. Urban IJA (1981) Intraseptal administration of vasopressin and oxytocin affects hippocampal electroencephalogram in rat. Exp Neurol 73:131–147CrossRefGoogle Scholar
  177. Van Heuven-Nolsen D, Versteeg DHG (1985) Interaction of vasopressin with the nigro-striatal dopamine system: site and mechanism of action. Brain Res 337:269–276PubMedCrossRefGoogle Scholar
  178. Van Heuven-Nolsen D, De Kloet ER, Versteeg DHG (1984 a) Oxytocin affects noradrenaline utilization in distinct limbic-forebrain regions of the rat brain. Neuropharmacology 23:269–276CrossRefGoogle Scholar
  179. Van Heuven-Nolsen D, De Kloet ER, Versteeg DHG (1984 b) Pro-Leu-GlyNH2 affects dopamine and noradrenaline utilization in rat limbic-forebrain nuclei. Brain Res 322:213–218PubMedCrossRefGoogle Scholar
  180. Van Ree JM (1982) Neurohypophyseal hormones and addiction. In: Yoshida H, Hagihara Y, Ebashi S (1982) Advances in pharmacology and therpeutics II, vol 1. CNS pharmacology. Neuropeptides. Pergamon, Oxford, pp 199–209Google Scholar
  181. Van Ree JM (1983) Neuropeptides and addictive behaviour. Alcohol Alcoholism 18:325–330Google Scholar
  182. Van Ree JM, De Wied D (1976) Prolyl-leucyl-glycinamide (PLG) facilitates morphine dependence. Life Sci 19:1331–1339PubMedCrossRefGoogle Scholar
  183. Van Ree JM, De Wied D (1977 a) Modulation of heroin self-administration by neurohypophyseal principles. Eur J Pharmacol 43:199–202PubMedCrossRefGoogle Scholar
  184. Van Ree JM, De Wied D (1977 b) Heroin self-administration is under control of vasopressin. Life Sci 21:315–320PubMedCrossRefGoogle Scholar
  185. Van Wimersma Greidanus TJB, Dogterom J, De Wied D (1975) Intraventricular administration of anti-vasopressin serum inhibits memory consolidation of rats. Life Sci 16:637–644Google Scholar
  186. Van Wimersma Greidanus TJB, Van Ree JM, Versteeg DHG (1980) Neurohypophyseal peptides and avoidance behavior: the involvement of vasopressin and oxytocin in memory processes. In: Ajmone Marsan C, Traczyk WZ (eds) Neuropeptides and neural transmission. Raven, New York, pp 293–300Google Scholar
  187. Van Wimersma Greidanus TJB, Bohus B, Kovács GL, Versteeg DHG, Burbach JHP, De Wied D (1983) Sites of behavioral and neurochemical action of ACTH-like peptides and neurohypophyseal hormones. Neurosci Biobehav Rev 7:453–463PubMedCrossRefGoogle Scholar
  188. Versteeg DHG (1983) Neurohypophyseal hormones and brain neurochemistry. Pharmacol Ther 19:297–325CrossRefGoogle Scholar
  189. Versteeg DHG, Tanaka M, De Kloet ER, Van Ree JM, De Wied D (1978) Prolyl-leucyl- glycinamide (PLG): regional effects on α-MPT-induced catecholamine disappearance in rat brain. Brain Res 143:561–566PubMedCrossRefGoogle Scholar
  190. Walter R, Hoffmann PL, Flexner JB, Flexner LB (1975) Neurohypophyseal hormones, analogs and fragments: their effect on puromycin-induced amnesia. Proc Natl Acad Sci (USA) 72:4180–4184CrossRefGoogle Scholar
  191. Walter R, Van Ree JM, De Wied D (1978) Modification of conditioned behavior of rats by neurohypophyseal hormones and analogues. Proc Natl Acad Sci (USA) 75:2493–2496CrossRefGoogle Scholar
  192. Way EL, Rezvani A (1984) Opiate tolerance and physical dependence: assessment and mechanisms. In: Hughes J, Collier HOJ, Rance MJ, Tyers MB (eds) Opioids past, present and future. Taylor and Francis, London, pp 103–108Google Scholar
  193. Wikler A (1980) Opioid dependence. Mechanism and treatment. Plenum, New YorkGoogle Scholar
  194. Xiao X, Veldhuis HD, Van Ree JM (1984) Neuropeptides related to neurohypophyseal hormones interfere with apomorphine-induced behavioral changes. Neuropeptides 4:237–245PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1986

Authors and Affiliations

  • G. L. Kovács
    • 1
  1. 1.Institute of PathophysiologyUniversity Medical SchoolSzegedHungary

Personalised recommendations