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Morphine-induced inhibition of different pain responses in relation to the regional turnover of rat brain noradrenaline and dopamine

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Abstract

The influence of morphine on different pain reactions integrated at different levels of the central nervous system was studied in rats together with the determination of the turnover rate of noradrenaline and dopamine in discrete areas of the brain.

Morphine was found to increase the thresholds for vocalisation and vocalisation afterdischarge leaving the threshold for motor response unaffected. The effect of morphine on the threshold for vocalisation was found to be antagonized by naloxone and yohimbine and increased by α-methyl-p-tyrosine, FLA 63, phenoxybenzamine, chlorpromazine and pimozide. The effects on the threshold for vocalisation afterdischarge were antagonized by naloxone, and reduced by α-methyl-p-tyrosine, pimozide and chlorpromazine and were enhanced by phenoxybenzamine and yohimbine. Atropine did not change the morphine effect on either threshold. Morphine (5 mg/kg s.c.) was found to increase the turnover rate of dopamine in the telencephalic cortex and the diencephalons-mesencephalon-striatum and that of noradrenaline in the medulla oblongata-pons region. Both increases were antagonized by naloxone.

The ability of morphine to increase the threshold for vocalisation afterdischarge (proposed to reflect the emotional component of pain reactions) is suggested to be closely related to the increased turnover of dopamine in limbic structures of the brain, most probably by an increased release of this transmitter. The effect of morphine on the threshold for vocalisation remains to be evaluated but a decreased activity of noradrenaline and dopamine neurotransmission was found to increase the morphine effect on this threshold.

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References

  • Andén, N.-E., Butcher, S. G., Corrdoi, H., Fuxe, K., Ungerstedt, U.: Recptor activity and turnover of dopamine and noradrenaline after neuroleptics. Europ. J. Pharmacol. 11, 303–314 (1970)

    Google Scholar 

  • Andén, N.-E., Corrodi, H., Dahlström, A., Fuxe, K., Hökfelt, T.: Effects of tyrosine hydroxylase inhibition on the amine levels of central monoamine neurons. Life Sci. 5, 561–568 (1966)

    Google Scholar 

  • Andén, N.-E., Strömbom, U.: Adrenergic receptor blocking agents: Effects on central noradrenaline and dopamine receptors and on motor activity. Psychopharmacologia (Berl.) 38, 91–103 (1974)

    Google Scholar 

  • Anderson, C., Stone, T. W.: On the mechanism of action of clonidine: Effects on single central neurones. Brit. J. Pharmacol. 51, 359–365 (1974)

    Google Scholar 

  • Ayhan, I. H.: Effect of 6-hydroxydopamine on morphine analgesia. Psychopharmacologia (Berl.) 25, 183–188 (1972)

    Google Scholar 

  • Beecher, H. K.: In: The measurement of subjective responses: quantitative effects of drugs. New York: Oxford University Press 1959

    Google Scholar 

  • Bhargava, H. N., Afifi, A. H., Way, E. L.: Effect of chemical sympathectomy on morphine antinociception and tolerance development in the rat. Biochem. Pharmacol. 22, 2769–2772 (1973)

    Google Scholar 

  • Bhargava, H. N., Way, E. L.: Effect of 1-phenyl-3-(2-thiazalyl)-2-thiourea, a dopamine Β-hydroxylase inhibitor, on morphine analgesia, tolerance and physical dependence. J. Pharmacol. exp. Ther. 190, 165–175 (1974)

    Google Scholar 

  • BlÄsig, J., Reinhold, K., Herz, A.: Effect of 6-hydroxydopamine, 5,6-dihdroxytryptamine and raphe lesions on the antinociceptive actions of morphine in rats. Psychopharmacologia (Berl.) 31, 111–119 (1973)

    Google Scholar 

  • Bolme, P., Corrodi, H., Fuxe, K., Hökfelt, T., Lidbrink, P., Goldstein, M.: Possible involvement of central adrenaline neurons in vasomotor and respiratory control. Studies with clonidine and its interactions with piperoxane and yohimbine. Europ. J. Pharmacol. 28, 89–94 (1974)

    Google Scholar 

  • Brodie, B. B., Costa, E., Dlabac, A., Neff, N. H., Smookler, H. H.: Application of Steady State Kinetics to the estimation of synthesis rate and turnover time of tissue catecholamines. J. Pharmacol. exp. Ther. 154, 493–498 (1966)

    Google Scholar 

  • Buxbaum, D. M., Yarbrough, G. G., Carter, M. E.: Biogenic amines and narcotic effects. 1. Modification of morphine-induced analgesia and motor activity after alteration of cerebral amine levels. J. Pharmacol. exp. Ther. 185, 317–327 (1973)

    Google Scholar 

  • Cahn, J., Herold, M.: Pain and psychotropic drugs. In: Pain. A. Soulairac, J. Cahn and J. Charpentier, eds., pp. 335–371. London-New York: Academic Press 1968

    Google Scholar 

  • Carlsson, A., Corrodi, H., Fuxe, K., Hökfelt, T.: Effects of some antidepressant drugs on the depletion of intraneuronal brain catecholamine stores caused by 4-α-dimethyl-metatyramine. Europ. J. Pharmacol. 5, 367–373 (1969)

    Google Scholar 

  • Carlsson, A., Lindqvist, M.: Effect of chlorpromazine or haloperidol on formation of 3-methoxytyramine and nor-metanephrine in mouse brain. Acta pharmacol. (Kbh.) 20, 140–144 (1963)

    Google Scholar 

  • Carrol, M. N., Lim, R. K. S.: Observations on the neuropharmacology of morphine and morphine-like analgesia. Arch. int. Pharmacodyn. 125, 383–403 (1960)

    Google Scholar 

  • Cicero, T. J., Meyer, E. R., Smithloff, B. R.: Alpha adrenergic blocking agents: antinociceptive activity and enhancement of morphine-induced analgesia. J. Pharmacol. exp. Ther. 189, 72–82 (1974)

    Google Scholar 

  • Clouet, D. H., Ratner, M.: Catecholamine biosynthesis in brains of rats treated with morphine. Science 168, 854–856 (1970)

    Google Scholar 

  • Elchisak, M. A., Rosecrans, J. A.: Effect of central catecholamine depletions by 6-hydroxydopamine on morphine antinociception in rats. Res. Comm. Chem. Path. Pharm. 6, 349–352 (1973)

    Google Scholar 

  • Ernst, A. M.: Mode of action of apomorphine and dexamphetamine on gnawing compulsions in rats. Psychopharmacologia (Berl.) 10, 316–326 (1967)

    Google Scholar 

  • Fennessy, M. R., Lee, J. R.: Comparison of the dose-response effects of morphine on brain amines, analgesia and activity in mice. Brit. J. Pharmacol. 45, 240–248 (1972)

    Google Scholar 

  • Fischer, E., Heller, B., Lumbreras, N.: Influence of anticholinergic-antiparkinsonian agents on the effects of narcoanalgesic drugs in the rat. Experientia (Basel) 29, 188–189 (1973)

    Google Scholar 

  • 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 

  • Gunne, L. M.: Noradrenaline and adrenaline in the rat brain during acute and chronic morphine administration and during withdrawal. Nature (Lond.) 184, 1950–1951 (1959)

    Google Scholar 

  • Görlitz, B.-D., Frey, H.-H.: Central monoamines and antinociceptive drug action. Europ. J. Pharmacol. 20, 171–180 (1972)

    Google Scholar 

  • Hoffmeister, F.: On the possible relations between post-ganglionic adrenergic and cholinergic neurone blockade demonstrable in the peripheral autonomous nervous system and central analgesia. In: Pain. A. Soulairac, J. Cahn and J. Charpentier, eds., pp. 281–296. London-New York: Academic Press 1968

    Google Scholar 

  • Hoffmeister, F., Kroneberg, G.: Experimental studies in animals on the differentiation of analgesic activity. In: Methods in drug evaluation. P. Mantegazza and F. Piccinini, eds., pp. 270–277. Amsterdam: North Holland Publ. Co. 1966

    Google Scholar 

  • Korf, J., Bunney, B. S., Aghajanian, G. K.: Noradrenergic neurons: morphine inhibition of spontaneous activity. Europ. J. Pharmacol. 25, 165–169 (1974)

    Google Scholar 

  • Kuschinsky, K., Hornykiewicz, O.: Morphine catalepsy in the rat: Relation to striatal dopamine metabolism. Europ. J. Pharmacol. 19, 119–122 (1972)

    Google Scholar 

  • Kuschinsky, K., Hornykiewicz, O.: Effects of morphine on striatal dopamine metabolism: possible mechanism of its opposite effect on locomotor activity in rats and mice. Europ. J. Pharmacol. 26, 41–50 (1974)

    Google Scholar 

  • Major, C. T., Pleuvry, B. J.: Effects of α-methyl-p-tyrosine, p-chlorophenylalanine, 1-Β(3,4-dihydroxyphenyl) alanine, 5-hydroxytryptophan and diethyldithiocarbamate on the analgesic activity of morphine and methylamphetamine in the mouse. Brit. J. Pharmacol. 42, 512–521 (1971)

    Google Scholar 

  • Nakamura, K., Kuntzman, R., Maggio, A. C., Augulis, V., Conney, A. H.: Influence of 6-hydroxydopamine on the effect of morphine on the tail-flick latency. Psychopharmacologia (Berl.) 31, 177–189 (1973)

    Google Scholar 

  • Nickerson, M., Hollenberg, N. K.: Blockade of α-adrenergic receptors. In: Physiological pharmacology, vol. IV, W. S. Root and F. G. Hofmann, eds., pp. 243–305. New York-London: Academic Press 1967

    Google Scholar 

  • Paalzow, L.: Studies on the relationship between the analgesic activity of salicylic acid and the brain catecholamines in mice. Acta pharmacol. (Kbh.) 32, 11–21 (1973)

    Google Scholar 

  • Paalzow, L.: Analgesia produced by clonidine in mice and rats. J. Pharm. Pharmacol. 26, 361–363 (1974)

    Google Scholar 

  • Paalzow, L., Paalzow, G.: Studies on the relationship between morphine analgesia and the brain catecholamines in mice. Acta pharmacol. (Kbh.) 30, 104–114 (1971)

    Google Scholar 

  • Paalzow, G., Paalzow, L.: The effects of caffeine and theophylline on nociceptive stimulation in the rat. Acta pharmacol. (Kbh.) 32, 22–32 (1973)

    Google Scholar 

  • Paalzow, G., Paalzow, L., Stalby, B.: Pentazocine analgesia and regional rat brain catecholamines. Europ. J. Pharmacol. 27, 78–88 (1974)

    Google Scholar 

  • Reinhold, K., BlÄsig, J., Herz, A.: Changes in brain concentration of biogenic amines and the antinociceptive effect of morphine in rats. Naunyn-Schmiedeberg's Arch. Pharmacol. 278, 69–80 (1973)

    Google Scholar 

  • Saarnivara, L.: Analgesic activity of some sympathetic drugs and their effect on morphine analgesia in rabbits. Ann. Med. exp. Fenn. 47, 180–190 (1969)

    Google Scholar 

  • Samanin, R., Bernasconi, S.: Effects of intraventricularly injected 6-OH dopamine on midbrain raphe lesion on morphine analgesia. Psychopharmacologia (Berl.) 25, 175–182 (1972)

    Google Scholar 

  • Schellenberger, 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 

  • Schmitt, H., Le Douarec, J.-C, Petillot, N.: Antagonism of the antinociceptive action of xylazine, an α-sympathomimetic agent, by adrenoceptor and cholinoceptor blocking agents. Neuropharmacology 13, 295–303 (1974)

    Google Scholar 

  • Smith, C. B., Villarreal, J. E., Bednarczyk, J. H., Scheldon, M. I.: Tolerance to morphine induced increases in 14C catecholamine synthesis in mouse brain. Science 170, 1106–1108 (1970)

    Google Scholar 

  • Sokal, R. R., Rohlf, F. J.: Biometry. San Francisco: Freeman 1969

    Google Scholar 

  • Starke, K.: Regulation of catecholamine release: α-Receptor mediated feed-back control in peripheral and central neurones. In: Frontiers in catecholamine research. E. Usdin and S. S. Snyder, eds., pp. 561–565. New York-Toronto-Oxford-Sydney-Braunschweig: Pergamon Press 1973

    Google Scholar 

  • Watanabe, K., Matsui, Y., Iwata, H.: Enhancement of the analgesic effect of morphine by sodium diethyldithiocarbamate in rats. Experientia (Basel) 25, 950–951 (1969)

    Google Scholar 

  • Vedernikov, Y. P., Afrikanov, J. J.: On the role of adrenergic mechanism in morphine analgesic action. J. Pharm. Pharmacol. 21, 845–847 (1969)

    Google Scholar 

  • Verri, R. A., Graeff, F. G., Corrado, A. P.: Effect of reserpine and alphamethyltyrosine on morphine analgesia. Int. J. Neuropharmacol. 7, 283–292 (1968)

    Google Scholar 

  • Vogt, M.: The concentration of sympathin in different parts of the central nervous system under normal conditions and after the administration of drugs. J. Physiol. (Lond.) 123, 451–481 (1954)

    Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutical Pharmacology, Biomedical Center, University of Uppsala, Uppsala

    Gudrun Paalzow & Lennart Paalzow

  2. Centrallaboratoriet, Apoteksbolaget AB, Solna, Sweden

    Gudrun Paalzow & Lennart Paalzow

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  1. Gudrun Paalzow
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  2. Lennart Paalzow
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Paalzow, G., Paalzow, L. Morphine-induced inhibition of different pain responses in relation to the regional turnover of rat brain noradrenaline and dopamine. Psychopharmacologia 45, 9–20 (1975). https://doi.org/10.1007/BF00426204

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  • DOI: https://doi.org/10.1007/BF00426204

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