Abstract
The effects of selective agonists for δ opioid receptors: [D-Thr2, Leu5]-enkephalyl-Thr6 (DTLET) and μ receptors: [D-Ala2, MePhe4, Gly-ol5]-enkephalin (DAGO) and of (R)-3-(N-hydroxyl-carboxamido-2-benzylpropanoyl)-L-alanine (kelatorphan), a complete inhibitor of enkephalin degrading enzymes, on the motor activity of rats was examined after their local administration into the nucleus accumbens (NA) or nucleus caudatus (NC). In both structures DTLET dose dependently enhanced locomotor activity as measured in the open-field test. This strong effect was reversed by the selective δ antagonist: ICI 174,864. Contrastingly, DAGO induced hypoactivity followed by hyperactivity 150 min later. This biphasic effect was blocked by systemic injection of naloxone, but not by ICI 174,864. The physiological relevance of these effects was ascertained by the naloxone-reversible stimulatory responses induced by kelatorphan, supporting a role for endogenous enkephalins in the control of behavior through δ receptor stimulation.
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Babbini M, Davis WM (1972) Time dose relationships for locomotor activity effects of morphine after acute or repeated treatment. Br J Pharmacol 46:213–224
Brady LS, Holtzman SG (1981) Effects of intraventricular morphine and enkephalins on locomotor activity in non-dependent, morphine-dependent and post-dependent rats. J Pharmacol Exp Ther 218:613–620
Broekkamp CLE, Phillips AG, Cools AT (1979) Stimulant effects of enkephalin microinjection into the dopaminergic A10 area. Nature 278:560–562
Browne RG, Segal DS (1978) β-endorphin and opiate-induced immobility: behavioral caracterization and tolerance development. In: Van Ree JM, Terenius L (eds) Characteristics and functions of opioids. Elsevier/North-Holland Biomedical Press, Amsterdam, pp 413–414
Buxbaum DM, Yarborough GG, Carter ME (1973) Biogenic amines and narcotic effects. I-Modification of morphine-induced analgesia and motor activity after activation of cerebral amine levels. J Pharmacol Exp Ther 185:317–327
Costall B, Fortune DH, Naylor RJ (1978) The induction of catalepsy and hyperactivity by morphine administered directly into the nucleus accumbens of rats. Eur J Pharmacol 49:49–64
Cotton R, Giles MG, Miller L, Show JS, Timms D (1984) ICI 174,864: a highly selective antagonist for the opioid δ receptor. Eur J Pharmacol 97:331–332
Cowan AC, Rance MJ, Blackburn TP (1986) In vivo studies on delta opioid receptors. In: Holaday JW, Law PY, Herz A (eds) Progress in opioid research INRC. NIDA Res Monogr 75, pp 473–476
Crawley JN, Hommer DW, Skirboll LR (1984) Behavioral and neurophysiological evidence for a facilitatory interaction between co-existing transmitters: cholecystokinin and dopamine. Neurochem Int 6:755–760
Domino EF, Vasko MR, Wilson AE (1976) Mixed depressant and stimulant actions of morphine and their relationship to brain acetylcholine. Life Sci 18:361–376
Esposito RU, Kornetsky C (1978) Opioids and rewarding brain stimulation. Neurosci Biobehav Rev 2:115–122
Fournié-Zaluski MC, Chaillet P, Bouboutou R, Coulaud A, Chérot P, Waksman G, Costentin J, Roques BP (1984) Analgesic effects of kelatorphan, a new highly potent inhibitor of multiple enkephalin degrading enzymes. Eur J Pharmacol 102:525–528
Geula C, Asdourian D (1985) Asymetric behavior induced by enkephalinergic agents in the basal ganglia. Pharmacol Biochem Behav 23:207–213
Handa BK, Lane AC, Lord JAH, Morgan BA, Rance MJ, Smith CFC (1981) Analogues of beta-LPH 61–64 possessing selective agonists of mu-opiate receptors. Eur J Pharmacol 70:531–540
Havemann U, Kuschinsky K (1985) Locomotor activity of rats after injection of various opioids into the nucleus accumbens and the septum medial. Naunyn Schmiedeberg's Arch Pharmacol 331:175–180
Herkenham M, Pert CB (1980) In vitro autoradiography of opiate receptors in rat brain suggests loci of “opiatergic” pathways. Proc Natl Acad Sci USA 77:5532–5536
Iversen SD, Iversen LL (1981) Drugs affecting mood: antidepressants and opiates. In: Iversen SD, Iversen LL (eds) Behavioral Pharmacology (2nd edn). Oxford University Press, Oxford, pp 194–230
Joyce EM, Koob GF, Strecker R, Iversen SD, Bloom FE (1981) The bahavioural effects of enkephalin analogues injected into the ventral tegmental area and globus pallidus. Brain Res 221:359–370
Kalivas PW, Bronson M (1985) Mesolimbic dopamine lesions produce an augmented behavioral response of enkephalin. Neuropharmacology 24:931–936
Kalivas PW, Miller JS (1984) Neurotensin neurons in the ventral tegmental area project to the medial nucleus accumbens. Brain Res 300:157–160
Kalivas PW, Richardson-Carlson R (1986) Endogenous enkephalin modulation of dopamine neurons in ventral tegmental area. Am J Physiol 251:R243
Kalivas PW, Nemeroff CB, Prange AJ Jr (1982) Neuroanatomical sites of action of neurotensine. Ann NY Acad Sci 400:307–318
Kalivas PW, Widerlöv E, Stanley D, Breese G, Prange AJ Jr (1983) Enkephalin action on the mesolimbic system. A dopamine-dependent and a dopamine-independent increase in locomotor activity. J Pharmacol Exp Ther 227:229–237
Locke KW, Holtzman SG (1986) Behavioral effects of opioid peptides selective for mu or delta receptors. I-Morphine like discriminative stimulus effects. J Pharmacol Exp Ther 238:990–995
Lord JAH, Waterfield AA, Hughes J, Kosterlitz HW (1977) Endogenous opioid peptides: mutliple agonists and receptors. Nature 267:495–499
Martin WR (1983) Pharmacology of opioids. Pharmacol Rev 35:283
Oka T, Hosoya E (1976) Effects of humoral modulators and naloxone on morphine induced changes in the spontaneous locomotor activity of the rat. Psychopharmacology 47:243–248
Paterson SJ, Robson LE, Kosterlitz HW (1984) Opioid receptors. In: Udenfriend S, Meienhofer T (eds) The peptides. Analysis, synthesis, biology, vol 6. Academic Press, New York London, pp 147–188
Paxinos G, Watson C (1982) The rat brain. Academic Press, New York
Pert A, Sivit C (1977) Neuroanatomical focus for morphine and enkephalin-induced hypermotility. Nature 265:645–647
Quirion R, Zajac JM, Morgat JL, Roques BP (1983) Autoradiographic distribution of mu and delta opiate receptors in rat brain using highly selective ligands. Life Sci 33:227–230
Roques BP (1986) Pharmacologie des différentes classes de récepteurs opioides cérébraux. Ann Endocrinol (Paris) 47:88–96
Roques BP, Fournié-Zaluski MC, Soroca E, Lecomte JM, Malfroy B, Llorens C, Schwartz JC (1980) The enkephalinase inhibitor thiorphan shows antinociceptive activity in mice. Nature 288:286–288
Roques BP, Daugé V, Gacel G, Fournié-Zaluski MC (1985) Selective agonists and antagonists of delta opioid receptors and inhibitors of enkephalins metabolism. Potential use in treatment of mental illness. Biol Psychiatry 7:287–289
Segal DS, Browne RG, Arnsten A, Derrington DC, Bloom FE, Davis AV, Guillemin R, Ling N (1979) Characterization of β-endorphin induced behavioral activation and immobilization. In: Usdin E, Bunney WE, Kline NS (eds) Endorphins in mental health research. Oxford University Press, New York, pp 307–324
Stein L, Belluzi JD (1978) Brain endorphins and sense of well-being: A psychobiological hypothesis. In: Costa E, Trabucchi (eds) Advances in biochemical pharmacology, vol. 18. Raven Press, New York, pp 299–311
Stinus L (1982) Interaction entre systèmes peptidergiques opioides et neurones dopaminergiques mésolimbiques: analyse comportementale. Actualités de Chimie Thérapeutique, 2ème série, Technique et Documentation Lavoisier, pp 275–284
Stinus L, Nadaud D, Jauregui J, Kelley AE (1986) Chronic treatment with five different neuroleptics elicits behavioral supersensitivity to opiate infusion into the nucleus accumbens. Biol Psychiatry 21:34–48
Tortella FC, Moreton JE, Khazan N (1978) Electroencephalographic and behavioral effects of D-Ala2-methionine-enkephalinamide and morphine in the rat. J Pharmacol Exp Ther 206:636–643
Turner AJ, Matsas R, Kenny AJ (1985) Are there neuropeptide specific peptidases? Biochem Pharmacol 34:1347–1356
Van Ree JM, Gaffori O, De Wied D (1983) In rats, the behavioral profile of CCK8 related peptides ressembles that of antipsychotic agents. Eur J Pharmacol 93:63–78
Waksman G, Hamel E, Fournié-Zaluski MC, Roques BP (1986) Autoradiographic comparison of the distribution of the neutral endopeptidase “enkephalinase” and of μ and δ opioid receptors in rat brain. Proc Natl Acad Sci USA 83:1523–1527
Walker JM, Berntson GG, Dandman CA, Coy DH, Schally AV, Kastin AJ (1977) An analog of enkephalin having prolonged opiate-like effects in vivo. Science 196:85–87
Walker JM, Berntson GG, Paulucci TS, Champney TC (1980) Blockade of endogenous opiates reduces activity in the rat. Pharmacol Biochem Behav 14:113–116
Winkler M, Havemann U, Kuschinsky K (1982) Unilateral injection of morphine into the nucleus accumbens induces akinesia and catalepsy but no spontaneous muscular rigidity in rats. Naunyn Schmiedeberg's Arch Pharmacol 318:143–147
Zajac JM, Gacel G, Petit F, Dodey P, Rossignol P, Roques BP (1983) Deltakephalin, Tyr-D-Thr-Gly-Phe-Leu-Thr: a new highly potent and fully specific agonist for opiate delta receptors. Biochem Biophys Res Commun 111:390–397
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Dauge, V., Rossignol, P. & Roques, B.P. Comparison of the behavioural effects induced by administration in rat nucleus accumbens or nucleus caudatus of selective μ and δ opioid peptides or kelatorphan an inhibitor of enkephalin-degrading-enzymes. Psychopharmacology 96, 343–352 (1988). https://doi.org/10.1007/BF00216060
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DOI: https://doi.org/10.1007/BF00216060