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Naloxone-precipitated withdrawal reveals sensitization to neurotransmitters in morphine tolerant/dependent rats

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Summary

Morphine tolerant/dependent rats were tested for their sensitivity to putative neurotransmitters or other receptor agonists injected intracerebroventricularly (i.c.v.) during naloxone-precipitated withdrawal. Dopamine, apomorphine, clonidine and serotonin were found to reinitiate withdrawal jumping behaviour when injected 30 min after naloxone. Dopamine and apomorphine also reinitiated jumping, but of a lesser intensity, when injected 3 h after naloxone-precipitated withdrawal. I.c.v. injection of acetylcholine or prostaglandin E1 failed to reinitiate withdrawal jumping. In addition, all the above substances failed to induce jumping behaviour in naive rats or in morphine tolerant/dependent rats before naloxone-precipitated withdrawal. Morphine tolerance and dependence therefore appears to be associated with changes in the sensitivity of the CNS to putative neurotransmitter substances. These changes are best demonstrated during the sudden termination of opiate action that is caused by administration of naloxone.

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References

  • Bläsig, J., Herz, A., Reinhold, K., Zieglgänsberger, S.: Development of physical dependence on morphine in respect to time and dosage and quantification of the precipitated withdrawal syndrome in rats. Psychopharmacologia (Berl.) 33, 19–38 (1973a)

    Google Scholar 

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

    Google Scholar 

  • Bradley, P. B., Dray, A.: The effects of microiontophoretically applied morphine and transmitter substances in rats during chronic treatment and after withdrawal from morphine. Br. J. Pharmacol. 51, 104–106 (1974)

    Google Scholar 

  • Brase, D. A., Tseng, L. F., Loh, H. H., Way, E. L.: Cholinergic modification of naloxone-induced jumping in morphine dependent mice. Eur. J. Pharmacol. 26, 1–8 (1974)

    Google Scholar 

  • Collier, H. O. J.: A general theory of the genesis of drug dependence by induction of receptors. Nature 205, 181–182 (1965)

    Google Scholar 

  • Eibergen, R. D., Carlson K. R.: Behavioral evidence for dopa minergic supersensitivity following chronic treatment with methadone or chlorpromazine in the guinea pig. Psychopharmacology 48, 139–146 (1976)

    Google Scholar 

  • Eidelberg, E., Erspamer, R.: Dopaminergic mechanisms of opiate actions in brain. J. Pharmacol. Exp. Ther. 192, 50–57 (1975)

    Google Scholar 

  • Fleming, W. W.: A comparative study of supersensitivity to norepinephrine and acetylcholine produced by denervation decentralization and reserpine. J. Pharmacol. Exp. Ther. 141, 173–179 (1963)

    Google Scholar 

  • Fleming, W. W., McPhilipps, J. J., Westfall, D. P.: Postjunctional supersensitivity and subsensitivity of excitable tissues to drugs. Ergebn. Physiol. 68, 55–119 (1973)

    Google Scholar 

  • Gianutsos, G., Hynes, M. D., Puri, S. K., Drawbaugh, R. B., Lal, H.: Effect of apomorphine and nigrostriatal lesions on aggression and striatal dopamine turnover during morphine withdrawal: evidence for dopaminergic supersensitivity in protracted abstinence. Psychopharmacologia (Berl.) 34, 37–44 (1974)

    Google Scholar 

  • Herz, A., Teschemacher, H. J.: Activities and sites of antinociceptive action of morphine-like analgesics. Adv. Drug Res. 6, 79–119 (1971)

    Google Scholar 

  • Jaffe, J. H., Sharpless, S. K.: Pharmacological denervation supersensitivity in the central nervous system: a theory of physical dependence. Proc Ass. Res. nerv. ment. Dis. 46, 226–246 (1968)

    Google Scholar 

  • Kuschinsky, K.: Does chronic morphine treatment induce a supersensitivity of dopamine receptors in rat brain? Psychopharmacologia (Berl.) 42, 225–229 (1975)

    Google Scholar 

  • Lagerspetz, K. Y. H., Varvikko, T., Tirri, R.: Effects of intraventricular brain injections of neurotransmitters on colonic temperature in morphine-tolerant rats. Life Sci. 15, 281–288 (1974)

    Google Scholar 

  • Medon, P. J., Blake, D. E.: Temperature effects of intraventricular serotonin, norepinephrine and pilocarpine in the morphinetolerant rat. Life Sci. 13, 1395–1402 (1973)

    Google Scholar 

  • Montel, H., Starke, K., Taube, H. D.: Morphine tolerance and dependence in noradrenaline neurones of the rat cerebral cortex. Naunyn-Schmiedeberg's Arch. Pharmacol. 288, 415–426 (1975)

    Google Scholar 

  • Puri, S. K., Lal, H.: Effect of dopaminergic stimulation or blockade on morphine-withdrawal aggression. Psychopharmacologia (Berl.) 32, 113–120 (1973)

    Google Scholar 

  • Satoh, M., Zieglgänsberger, W., Herz, A.: Supersensitivity of cortical neurones of the rat to acetylcholine and L-glutamate following chronic morphine treatment. Naunyn-Schmiedeberg's Arch. Pharmacol. 293, 101–103 (1976)

    Google Scholar 

  • Schulz, R., Goldstein, A.: Morphine tolerance and supersensitivity to 5-hydroxytryptamine in the myenteric plexus of the guineapig. Nature 244, 168–170 (1973)

    Google Scholar 

  • Schulz, R., Herz, A.: Aspects of opiate dependence in the myenteric plexus of the guinea-pig. Life Sci 19, 1117–1128 (1976)

    Google Scholar 

  • Smee, M. L., Overstreet, D. H.: Alterations in the effects of dopamine agonists and antagonists on general activity in rats following chronic morphine treatment. Psychopharmacology 49, 125–130 (1976)

    Google Scholar 

  • Starke, K.: Regulation of noradrenaline release by presynaptic receptor systems. Rev. Physiol. Biochem. Pharmacol 77, 1–124 (1977)

    Google Scholar 

  • Takayanagi, I., Sato, T., Takagi, K.: Action of 5-hydroxytryptamine on electrical activity of Auerbach's plexus in the ileum of the morphine dependent guinea-pig. Eur. J. Pharmacol. 27, 252–254 (1974)

    Google Scholar 

  • Trendelenburg, U.: Supersensitivity and subsensitivity to sympathomimetic amines. Pharmacol. Rev. 15, 225–276 (1963)

    Google Scholar 

  • Vasquez, B. J., Overstreet, D. H., Russel, R. W.: Psychopharmacological evidence for increase in receptor sensitivity following chronic morphine treatment. Psychopharmacologia (Berl.) 38, 287–302 (1974)

    Google Scholar 

  • Yarbrough, G. G.: Actions of acetylcholine and atropine on cerebral cortical neurons in chronically morphine treated rats. Life Sci. 15, 1523–1529 (1974)

    Google Scholar 

  • Żebrowska-Lupina, E., Przegalinski, M., Sloniec, M., Kleinrok, Z.: Clonidine-induced locomotor hyperactivity in rats: the role of central postsynaptic α-adrenoceptors. Naunyn-Schmiedeberg's Arch. Pharmacol. 297, 227–231 (1977)

    Google Scholar 

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Authors and Affiliations

  1. Abtelung für Neuropharmakologie, Max-Planck-Institut für Psychiatrie, Kraepelinstrasse 2, D-8000, München 40, Federal Republic of Germany

    Rüdiger Schulz & Albert Herz

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  1. Rüdiger Schulz
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  2. Albert Herz
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Schulz, R., Herz, A. Naloxone-precipitated withdrawal reveals sensitization to neurotransmitters in morphine tolerant/dependent rats. Naunyn-Schmiedeberg's Arch. Pharmacol. 299, 95–99 (1977). https://doi.org/10.1007/BF00508644

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  • DOI: https://doi.org/10.1007/BF00508644

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