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Psychopharmacology

, Volume 122, Issue 4, pp 374–378 | Cite as

Interaction of opioids with antidepressant-induced antinociception

  • F. Sierralta
  • H. F. Miranda
  • G. Pinardi
  • M. Mendez
Original Investigation

Abstract

The antinociceptive activity of antidepressant drugs is poorly understood. In this study, using the acetic acid writhing test in mice, the antinociception produced by clomipramine (CLO), maprotiline (MAP), imipramine (IMI), and zimelidine (ZIM) was tested and correlated with opioid drugs. All the compounds displayed a significant dose-dependent antinociception, which was not antagonized by naloxone (NX) or naltrexone (NTX). The administration of morphine (M) plus CLO, MAP, IMI or ZIM resulted in a significant additive effect that was antagonized by 1 or 10 mg/kg NX or NTX, except in the case of IMI. This finding suggests that the additive effect seems to be partially due to activation of opioid receptors, except for the case of imipramine. However, aminophylline, a non-selective blocker of A1/A2 adenosine receptors, significantly antagonized the antinociceptive activity of CLO, IMI, MAP and ZIM, demonstrating an interaction at the level of adenosine receptors. This work suggests that the antinociceptive activity of antidepressants could be dependent on critical levels of free 5-HT and NE at receptor(s) site(s) in CNS and on their interaction with opioid and adenosine receptors.

Key words

Antinociception Antidepressants Opioids Adenosine receptors 

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References

  1. Ardid D, Guilbaud G (1992) Antinociceptive effects of acute and “chronic” injections of tricyclic antidepressant drugs in a new model of mononeuropathy in rats. Pain 49:279–287CrossRefPubMedGoogle Scholar
  2. Bhargava HN, Larsen AK, Rahmani NH, Villar VM (1993) Naltrexone-induced alterations of the distribution of morphine in brain regions and spinal cord of the rat. Brain Res 607:1–8CrossRefPubMedGoogle Scholar
  3. Bergman SA, Wynn RL, Alvarez L, Asher K, Thut PD (1991) Imipramine-fentanyl antinociception in a rabbit booth pulp model. Life Sci 49:1279–1288CrossRefPubMedGoogle Scholar
  4. Biegon A, Samuel D (1980) Interaction of tricyclic antidepressants with opiate receptors. Biochem Pharmacol 29:460–462CrossRefPubMedGoogle Scholar
  5. Botney M, Fields HL (1983) Amitriptyline potentiates morphine analgesia by a direct action on the central nervous system. Ann Neurol 13:160–164CrossRefPubMedGoogle Scholar
  6. Carr DJ, Gerak LR, Franz CP (1994) Naltrexone antagonizes the analgesia and immunosuppressive effects of morphine in mice. J Pharmacol Exp Ther 269:693–698PubMedGoogle Scholar
  7. Committee for Research and Ethical Issues of the IASP (1983) Ethical standards for investigations of experimental pain in animals. Pain 16:109–110Google Scholar
  8. Crisp T, Stafinsky JL, Spanos LJ, Uram M, Perni VC, Donepudi HB (1991) Analgesic effects of serotonin and receptor-selective serotonin agonists in the rat spinal cord. Gen Pharmacol 22:247–251PubMedGoogle Scholar
  9. Daval JL, Nehlig A, Nicolas F (1991) Physiological and pharmacological properties of adenosine: therapeutic implications. Life Sci 49:1435–1453CrossRefPubMedGoogle Scholar
  10. Enna SJ, Kendall DA (1981) Interaction of antidepressants with brain neurotransmitter receptors. J Clin Psychopharmacol 1:12–16Google Scholar
  11. Fasmer OB, Kunskaar S, Hole K (1989) Antinociceptive effects of serotonergic reuptake inhibitors in mice. Neuropharmacology 28:1363–1366CrossRefPubMedGoogle Scholar
  12. Fuller RWG (1981) Enhancement of monoaminergic neurotransmission by antidepressant drugs. In: Enna SJ, Malick JB, Richelson E (eds) Antidepressants: neurochemicals, behavioral and clinical perspectives. Raven Press, New York, pp 1–12Google Scholar
  13. Goldstein FJ, Mojaverian P, Ossipov MH, Swamson BN (1982) Elevation in analgesic effect and plasma levels of morphine by desipramine in rats. Pain 14:279–282CrossRefPubMedGoogle Scholar
  14. Goldstein FJ, Malseed RT, Nutz JF (1990) Effects of chronic clomipramine on central DADLE antinociception. Pain 42:331–336CrossRefPubMedGoogle Scholar
  15. Hayashi G, Takemori AE (1971) The type of analgesic-receptor interaction involved in certain analgesic assays. Eur J Pharmacol 16:63–66CrossRefPubMedGoogle Scholar
  16. Ho IK, Loh HH, Way EL (1973) Cyclic adenosine monophosphate antagonism of morphine analgesia. J.Pharmacol Exp Ther 185:336–346PubMedGoogle Scholar
  17. Jensen TS, Yaksh TL (1984) Spinal monoamine and opiate systems partly mediate the antinociceptive effects produced by glutamate at brain stem sites. Brain Res 321:287–297CrossRefPubMedGoogle Scholar
  18. Jurna I (1981) Aminophylline differentiates between the depressants effects of morphine on the spinal nociceptive reflex and on the spinal ascending activity evoked from afferent C fibers. Eur J Pharmacol 71:393–400CrossRefPubMedGoogle Scholar
  19. Kilpatrick GJ, Bunce KT, Tyers MB (1990) 5-HT3 receptors. Med Res Rev 10:441–475PubMedGoogle Scholar
  20. Larsen JJ, Arnt J (1984) Spinal 5-HT or NA uptake inhibition potentiates supraspinal morphine antinociception in rats. Acta Pharmacol Toxicol 54:72–75Google Scholar
  21. Maggi A, U'Prichard DC, Enna SJ (1980) Differential effects of antidepressant treatment on brain monoaminergic receptors. Eur J Pharmacol 61:91–98CrossRefGoogle Scholar
  22. Magni G (1991) The use of antidepressants in the treatment of chronic pain. Drugs 42:730–748PubMedGoogle Scholar
  23. Ollat H, Parvez S, Parvez H (1989) Endogenous morphines and nociception. Biogenic Amines 6:381–410Google Scholar
  24. O'Neill KA, Valentino D (1986) Chronic desipramine attenuates morphine analgesia. Pharmacol Biochem Behav 24:155–158CrossRefPubMedGoogle Scholar
  25. Pick CG, Paul D, Eison MS, Pasternak GW (1992) Potentiation of opioid analgesia by the antidepressant nefazodone. Eur J Pharmacol 211:375–381CrossRefPubMedGoogle Scholar
  26. Reichenberg K, Gaillard-Plaza G, Montastruc JL (1985) Influence of naloxone on the antinociceptive effects of some antidepressant drugs. Arch Int Pharmacodyn Ther 275:78–85PubMedGoogle Scholar
  27. Reisine T, Soubrie P (1982) Loss of rat cerebral cortical opiates receptors following chronic desipramine treatment. Eur J Pharmacol 77:39–44CrossRefPubMedGoogle Scholar
  28. Rosenblatt MR, Reich J, Dehring D (1984) Tricyclic antidepressants in treatment of depression and chronic pain. Anesth Analg 63:1025–1032PubMedGoogle Scholar
  29. Sawynok J, Reid A (1992) Desipramine potentiates spinal antinociception by 5-hydroxytryptamine, morphine and adenosine. Pain 50:113–118CrossRefPubMedGoogle Scholar
  30. Sierralta F, Miranda HF (1993) Adenosine modulates the antinociceptive action of benzodiazepines. Gen Pharmacol 24:891–894PubMedGoogle Scholar
  31. Smits SE, Takemori AE (1970) Quantitative studies on the antagonism by naloxone of some narcotics and narcotic-antagonist analgesics. Br J Pharmacol 39:627–638PubMedGoogle Scholar
  32. Stirt JA (1983) Aminophylline may act as a morphine antagonist. Anaesthesia 38:275–278PubMedGoogle Scholar
  33. Taiwo YO, Fabian A, Pazoles CJ, Fields HL (1985) Potentiation of morphine antinociception by monoamine reuptake inhibitors in the rat spinal cord. Pain 21:329–337CrossRefPubMedGoogle Scholar
  34. Takemori AE, Kupferberg HJ, Miller JW (1969) Quantitative studies on the antagonism of morphine by nalorphine and naloxone. J Pharmacol Exp Ther 169:39–45PubMedGoogle Scholar
  35. Takemori AE, Larson DL, Portoghese PS (1981) The irreversible narcotic antagonist and reversible agonistic properties of the fumaramate methyl ester derivative of naltrexone. Eur J Pharmacol 70:445–451CrossRefPubMedGoogle Scholar
  36. Tura B, Tura SM (1990) The analgesic effect of tricyclic antidepressants. Brain Res 518:19–22CrossRefPubMedGoogle Scholar
  37. Tyers MB (1982) Studies on the antinociceptive activities of mixtures of mu and kappa opiate receptor agonists and antagonists. Life Sci 31:1233–1234CrossRefPubMedGoogle Scholar
  38. Valeri P, Pimpinella G, Morrone LA, Romanelli L (1991) Antinociceptive effects of trazodone and m-chlorophenyl-piperazine (mCPP) in mice: interaction with morphine. Gen Pharmacol 22:127–131PubMedGoogle Scholar
  39. Van Paag HM (1983) In search of the mode of action of antidepressants. Neuropharmacology 22:433–440CrossRefPubMedGoogle Scholar
  40. Ward SJ, Takemori AE (1983) Relative involvement of mu, kappa and delta receptor mechanisms in opiate-mediated antinociception in mice. J. Pharmacol Exp Ther 224:525–530PubMedGoogle Scholar
  41. Wong CL, Bentley GA (1978) Increased antagonist potency of naloxone caused by morphine pretreatment. Eur J Pharmacol 47:415–422CrossRefPubMedGoogle Scholar
  42. Yang SW, Zhang ZH, Chen JY, Xie YF, Qiao JT, Dafny N (1994) Morphine and norepinephrine-induced antinociception at the spinal level is mediated by adenosine. Neuroreport 5:1441–1444PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • F. Sierralta
    • 1
  • H. F. Miranda
    • 1
  • G. Pinardi
    • 2
  • M. Mendez
    • 2
  1. 1.Department of Pharmacology, Faculty of MedicineUniversidad de ChileSantiagoChile
  2. 2.Department of Experimental Medicine, Campus Occidente, Faculty of MedicineUniversidad de ChileSantiagoChile

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