Psychopharmacology

, Volume 52, Issue 1, pp 7–15 | Cite as

Effect of muscarinic cholinergic drugs on morphine-induced catalepsy, antinociception and changes in brain dopamine metabolism

  • Seppo Kaakkola
  • Liisa Ahtee
Animal Studies

Abstract

The effects of drugs acting on muscarinic cholinergic receptors on the catalepsy, antinociception and changes in rectal temperature and in brain dopamine metabolism induced by morphine were studied in Wistar rats. Scopolamine (0.3–30 mg/kg) was about three times as potent as atropine (1–30 mg/kg) in potentiating the cataleptic effect of morphine. Methylscopolamine and methylatropine did not alter the cataleptic effect of morphine. Pilocarpine (100 mg/kg) and arecoline (10 mg/kg) slightly but significantly and RS86 (20–40 mg/kg) clearly antagonized the morphine-catalepsy. RS86 antagonized the atropineinduced potentiation of morphine catalepsy. The antinocieptive effect of pilocarpine was additive and that of RS86 less than additive with morphine. The antimuscarinic compounds did not alter the antinociceptive effect of morphine. Antimuscarinic compounds enhanced the hypothermic effect of morphine, but none of the compounds studied altered the hyperthermic effect of morphine. The antimuscarinic drugs reduced the concentration of striatal homovanillic acid (HVA) in about same proportion in control and morphine-treated rats. Both the muscarinic compounds and morphine increased the concentration of striatal HVA, but when combined their effects were not significantly different from those of inorphine alone. Scopolamine antagonized and pilocarpine accelerated the morphine-induced increase in the rate of depletion of cerebral dopamine content. The present results show that the effects of muscarinic and antimuscarinic cholinergic drugs on the cataleptic effect of morphine were opposite to their effects on the catalepsy induced by neuroleptic compounds.

Key words

Morphine Muscarinic drugs Antimuscarinic drugs Catalepsy Antinociception Dopamine 

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References

  1. Ahtee, L.: Effect of cholinergic drugs on methadone-induced catalepsy and stereotypies in rats treated chronically with methadone. Europ. J. Pharmacol. 39, 203–213 (1976)Google Scholar
  2. Ahtee, L., Kaakkola, S.: Effects of drugs acting on cholinergic receptors on the catalepsy and stereotypies induced by morphine and methadone in rats. Satellite Symposium to 6th Internat. Congress of Pharmacology, Abstracts, pp. 20–21, Espoo, July 18–20, 1975Google Scholar
  3. Ahtee, L., Kääriäinen, I.: The effect of narcotic analgesics on the homovanillic acid content of rat nucleus caudatus. Europ. J. Pharmacol. 22, 206–208 (1973)Google Scholar
  4. Ahtee, L., Kääriäinen, I.: The role of dopamine in pilocarpineinduced catalepsy. Naunyn-Schmiedeberg's Arch. Pharmacol. 284, 25–38 (1974)Google Scholar
  5. Ahtee, L., Kääriäinen, I., Paasonen, M. K.: Effect of nalorphine and antiparkinsonian drugs on methadone-induced rigidity; relation to homovanillic acid content of nucleus caudatus. Ann. Med. exp. Fenn. 50, 180–185 (1972)Google Scholar
  6. Andén, N.-E.: Effects of oxotremorine and physostigmine on the turnover of dopamine in the corpus striatum and the limbic system. J. Pharm. Pharmacol. 26, 738–740 (1974)Google Scholar
  7. Andén, N.-E., Bédard, P.: Influences of cholinergic mechanisms on the function and turnover of brain dopamine. J. Pharm. Pharmacol. 23, 460–462 (1971)Google Scholar
  8. Bartholini, G., Pletscher, A.: Atropine-induced changes of cerebral dopamine turnover. Experientia (Basel) 27, 1302–1303 (1971)Google Scholar
  9. Cashin, C. H., Sutton, S.: The effect of anti-Parkinson drugs on catalepsy induced by α-methyl-p-tyrosine in rats pretreated with intraventricular 6-hydroxydopamine. Brit. J. Pharmacol. 47, 658P-659P (1973)Google Scholar
  10. Corrodi, H., Fuxe, K., Hammer, W., Sjöqvist, F., Ungerstedt, U.: Oxotremorine and central monoamine neurons. Life Sci. 6, 2557–2566 (1967)Google Scholar
  11. Corrodi, H., Fuxe, K., Lidbrink, P.: Interaction between choliergic and catecholaminergic neurons in rat brain. Brain Res. 43, 397–416 (1972)Google Scholar
  12. Costall, B., Naylor, R. J.: Modification of amphetamine effects by intracerebrally administered anticholinergic agents. Life Sci. 11, 239–253 (1972)Google Scholar
  13. Costall, B., Naylor, R. J.: Neuroleptic and non-neuroleptic catalepsy. Arzneimittel-Forsch 23, 674–683 (1973)Google Scholar
  14. Dahlström, B., Paalzow, G., Paalzow, L.: A pharmacokinetic approach to morphine analgesia and its relation to regional turnover of rat brain catecholamines. Life Sci 17, 11–16 (1975)Google Scholar
  15. Evans, W. O.: A new technique for the investigation of some analgesic drugs on a reflexive behavior in the rat. Psychopharmacologia (Berl.) 2, 318–325 (1961)Google Scholar
  16. Friedman, A., Everett, G. M.: Pharmacological aspects of parkinsonism. In: Advances in pharmacology, Vol. 3, S. Garattini and P. A. Shore, eds., pp. 83–127. New York-London: Academic Press 1964Google Scholar
  17. Fukui, K., Takagi, H.: Effect of morphine on the cerebral contents of metabolites of dopamine in normal and tolerant mice: its possible relation to analgesic action. Brit. J. Pharmacol. 44, 45–51 (1972)Google Scholar
  18. Gunne, L. M., Jonsson, J., Fuxe, K.: Effects of morphine intoxication on brain catecholamine neurons. Europ. J. Pharmacol 5, 338–342 (1969)Google Scholar
  19. Herz, A.: Über die Beeinflussung zentral dämpfender und erregender Morphinwirkungen durch Anticholinergica, Nicotinolytica und Antihistaminica an der Ratte. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 241, 236–253 (1961)Google Scholar
  20. Herz, A.: Wirkungen des Arecolins auf das Zentralnervensystem. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 242, 414–429 (1962)Google Scholar
  21. Herz, A., Metyš, J.: Inhibition of nociceptive responses by substances acting on central cholinoceptive systems. In: Pain, A. Soulairac, J. Cahn, and J. Charpentier, eds., pp. 321–334. New York-London: Academic Press 1968Google Scholar
  22. Houser, V. P., Van Hart, D. A.: The effects of scopolamine and pilocarpine upon the aversive threshold of the rat. Pharmacol. Biochem. Behav. 1, 427–431 (1973)Google Scholar
  23. Howes, J. F., Harris, L. S., Dewey, W. L., Voyda, C. A.: Brain acetylcholine levels and inhibition of the tail-flick reflex in mice. J. Pharmacol. exp. Ther. 169, 23–28 (1969)Google Scholar
  24. Ireson, J. D.: A comparison of the antinociceptive actions of cholinomimetic and morphine-like drugs. Brit. J. Pharmacol. 40, 92–101 (1970)Google Scholar
  25. Jacob, J., Barthelemy, C.: Antinociceptive effects of morphine and central cholinergic systems. In: Pain, R. Janzen, W. D. Keidel, A. Herz, and C. Steichele, eds., pp. 236–239, Stuttgart: Thieme 1972Google Scholar
  26. Kaakkola, S., Ahtee, L.: Effect of anticholinergics and cholinomimetics on morphine-catalepsy in rats. 6th Internat. Congress of Pharmacology, Abstracts, p. 270, Helsinki, Finland, July 20–25, 1975Google Scholar
  27. Koelle, G. B.: Parasympathomimetic agents. In: The pharmacological basis of therapeutics, 5th ed., L. S. Goodman and A. Gilman, eds., pp. 467–476, New York: MacMillan 1975Google Scholar
  28. Kuschinsky, K.: Evidence that morphine increases dopamine utilization in corpora striata of rats. Experientia (Basel) 29, 1365–1366 (1973)Google Scholar
  29. Kuschinsky, K.: Are cholinergic mechanisms involved in morphine effects on motility? Naunyn-Schmiedeberg's Arch. Pharmacol. 281, 167–173 (1974)Google Scholar
  30. Kuschinsky, K., Hornykiewicz, O.: Morphine catalepsy in the rat: relation to striatal dopamine metabolism. Europ. J. Pharmacol. 19, 119–122 (1972)Google Scholar
  31. Kääriäinen, I., Vikberg, P.: Effects of aminooxyacetic acid and baclofen on catalepsy, striatal homovanillic acid increase and antinociception caused by methadone in rats. Acta pharmacol. (Kbh.) 39, 536–544 (1976)Google Scholar
  32. Laverty, R., Sharman, D. F.: Modification by drugs of the metabolism of 3,4-dihydroxyphenylethylamine, noradrenaline and 5-hydroxytryptamine in the brain. Brit. J. Pharmacol. 24, 759–772 (1965)Google Scholar
  33. Lotti, V. J.: Body temperature responses to morphine. In: The pharmacology of thermoregulation. Symp., E. Schönbaum and P. Lomax, eds., pp. 382–394. Basel: Karger 1973Google Scholar
  34. Morpurgo, C.: Effects of antiparkinson drugs on phenthiazineinduced catonic reaction. Arch. int. Pharmacodyn. 137, 84–90 (1962)Google Scholar
  35. Nose, T., Takemoto, H.: Effect of oxotremorine on homovanillic acid concentration in the striatum of the rat. Europ. J. Pharmacol. 25, 51–55 (1974)Google Scholar
  36. O'Keeffe, R., Sharman, D. F., Vogt, M.: Effect of drugs used in psychoses on cerebral dopamine metabolism. Brit. J. Pharmacol. 38, 287–304 (1970)Google Scholar
  37. Parkes, M. W.: An examination of central actions characteristic of scopolamine: comparison of central and peripheral activity in scopolamine, atropine and some synthetic basic esters. Psychopharmacologia (Berl.) 7, 1–19 (1965)Google Scholar
  38. Perez-Cuet, J., DiChiara, G., Gessa, G. L.: Accelerated synthesis of dopamine in the rat brain after methadone. Experientia (Basel) 28, 926 (1972)Google Scholar
  39. Pleuvry, B. J., Tobias, M. A.: Comparison of the antinociceptive activities of physostigmine, oxotremorine and morphine in the mouse. Brit. J. Pharmacol. 43, 706–714 (1971)Google Scholar
  40. Portig, P. J., Sharman, D. F., Vogt, M.: Release by tubocurarine of dopamine and homovanillic acid from the superfused caudate nucleus. J. Physiol. (Lond.) 194, 565–572 (1968)Google Scholar
  41. Puri, S. K., Reddy, C., Lal, H.: Blockade of central dopaminergic receptors by morphine: effect of haloperidol, apomorphine or benztropine. Res. Commun. Chem. Path. Pharmacol. 5, 389–401 (1973)Google Scholar
  42. Sasame, H. A., Perez-Cruet, J., DiChiara, G., Tagliamonte, A., Tagliamonte, P., Gessa, G. L.: Evidence that methadone blocks dopamine receptors in the brain. J. Neurochem. 19, 1953–1957 (1972)Google Scholar
  43. Sharman, D. F.: A discussion of the modes of action of drugs which increase the concentration of 4-hydroxy-3-methoxyphenylacetic acid (homovanillic acid) in the striatum of the mouse. Brit. J. Pharmacol. 30, 620–626 (1967)Google Scholar
  44. Shellenberger, M. K., Gordon, J. H.: A rapid, simplified procedure for simultaneous assay of norepinephrine, dopamine and 5-hydroxytryptamine from discrete brain areas. Analyt. Biochem. 39, 356–372 (1971)Google Scholar
  45. Simon, P., Malatray, J., Boissier, J. R.: Antagonism by amantadine of prochlorpemazine-induced catalepsy. J. Pharm. Pharmacol. 22, 546–547 (1970)Google Scholar
  46. Smelik, P. G., Ernst, A. M.: Role of nigro-neostriatal dopaminergic fibres in compulsive gnawing behavior in rats. Life Sci. 5, 1485–1488 (1966)Google Scholar
  47. Stadler, H., Lloyd, K. G., Gadea-Ciria, M., Bartholini, G.: Enhanced striatal acetylcholine release by chlorpromazine and its reversal by apomorphine. Brain Res. 55, 476–480 (1973)Google Scholar
  48. Sugrue, M. F.: The effects of acutely administered analgesics on the turnover of noradrenaline and dopamine in various regions of the rat brain. Brit. J. Pharmacol. 52, 159–165 (1974)Google Scholar
  49. Takemori, A. E., Tulunay, F. C., Yano, I.: Differential effects on morphine analgesia and naloxone antagonism by biogenic amine modifiers. Life Sci. 17, 21–28 (1975)Google Scholar
  50. Tulunay, F. C., Yano, I., Takemori, A. E.: The effect of biogenic amine modifiers on morphine analgesia and its antagonism by naloxone. Europ. J. Pharmacol 35, 285–292 (1976)Google Scholar
  51. Van Eick, A. J., Bock, J.: Comparison of analgesic, cholinomimetic, anticholinergic and sympathomimetic drugs by means of the hot-plate test. Arch. int. Pharmacodyn. 189, 384–387 (1971)Google Scholar
  52. Zetler, G.: Cataleptic state and hypothermia in mice, caused by central cholinergic stimulation and antagonized by anticholinergic and antidepressant drugs. Int. J. Neuropharmacol 7, 325–335 (1968)Google Scholar
  53. Yaksh, T. L., Yamamura, H. I.: Blockade by morphine of acetylcholine release from the caudate nucleus in the mid-pontine pretrigeminal cat. Brain Res 83, 520–524 (1975)Google Scholar

Copyright information

© Springer-Verlag 1977

Authors and Affiliations

  • Seppo Kaakkola
    • 1
  • Liisa Ahtee
    • 1
  1. 1.Department of PharmacologyUniversity of HelsinkiHelsinki 17Finland

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