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Psychopharmacology

, Volume 90, Issue 3, pp 408–411 | Cite as

Potentiation of disruptive effects of dextromethorphan by naloxone on fixed-interval performance in rats

  • Tambay Taşkin
Original Investigations

Abstract

A centrally acting antitussive agent dextromethorphan (DM) was tested to determine its possible interaction with naloxone in rats responding under a fixed-interval schedule of positive reinforcement. A sugar sweetened milk reward was used as a positive reinforcer. Under the same experimental conditions the effects of morphine alone and in combination with naloxone were also determined. Low dose DM (10 mg/kg) produced a slight increase, while higher doses (20–40 mg/kg) produced dose-dependent decreases in response rate. Morphine (0.3, 1.0 and 3.0 mg/kg) produced dose-dependent decreases in response rate. When doses of naloxone (0.1–1.0 mg/kg) were administered after the injection of DM the rate-decreasing effects of DM were potentiated even after the rate-increasing dose of naloxone (0.1 mg/kg) was used. When a dose of naloxone (0.1 mg/kg) was administered after the injection of morphine the rate-decreasing effects of morphine were markedly antagonized, i.e., the morphine dose-response curve was shifted to the right. The observed potentiation of DM disruption by naloxone on fixed-interval performance in rats is consistent with findings showing that naloxone potentiates the disruptive behavioral effects of a number of drugs that are psychotomimetic in man.

Key words

Dextromethorphan Morphine Naloxone Fixed-interval schedule Potentiation Rat 

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References

  1. Brady KT, Balster RL, May EL (1982) Stereoisomers of N-allylnormetazocine: Phencyclidine-like behavioral effects in squirrel monkeys and rats. Science 215:178–180Google Scholar
  2. Brady LS, Holtzman SG (1981) Effects of intraventricular morphine and enkephalins on schedule-controlled behavior in nondependent, morphine-dependent and post-dependent rats. J Pharmacol Exp Ther 219:344–357Google Scholar
  3. Chang KJ, Cuatrecasas P (1981) Heterogeneity and properties of opiate receptors. Fed Proc 40:2729–2734Google Scholar
  4. Commissaris R, Moore K, Rech R (1980) Naloxone potentiates the disruptive effects of mescaline on operant responding in the rat. Pharmacol Biochem Behav 13:601–603Google Scholar
  5. Craviso GL, Musacchio JM (1983a) High-affinity dextromethorphan binding sites in guinea pig brain. Mol Pharmacol 23:619–628Google Scholar
  6. Craviso GL, Musacchio JM (1983b) High-affinity dextromethorphan binding sites in guinea pig brain. Mol Pharmacol 23:629–640Google Scholar
  7. Dhawan BN, Gupta GP (1959) LSD-25 antagonism of morphine analgesia. Arch Int Pharmacodyn 123:132–139Google Scholar
  8. Dhawan BN, Gupta GP (1961) Antiemetic activity of D-lysergic acid diethylamide. J Pharmacol Exp Ther 133:137–139Google Scholar
  9. Domino EF (1964) Neurobiology of phencyclidine (sernyl), a drug with an unusual spectrum of pharmacologic activity. Int Rev Neurobiol 6:303–347Google Scholar
  10. Fertziger R, Fisher R (1977) Interaction between narcotic antagonists (naloxone) and lysergic acid diethylamide (LSD) in the rat. Psychopharmacology 54:313–314Google Scholar
  11. Hadorn DC, Anistranski JA, Connor JD (1984) Influence of naloxone on the effects of LSD in monkeys. Neuropharmacology 23:1297–1300Google Scholar
  12. Haertzen CA (1970) Subjective effects of narcotic antagonists cyclazocine and nalorphine on the Addiction Research Center Inventory (ARCI). Psychopharmacology 18:366–377Google Scholar
  13. Haigler HJ (1978) Morphine: effects of serotonergic neurons and neurons in areas with a serotonergic input. Eur J Pharmacol 51:361–376Google Scholar
  14. Haigler HJ, Spring DD (1979) Drugs that antagonize limb flick behavior induced by D-lysergic acid diethylamine (LSD) in cats. Psychopharmacolgy 64:31–34Google Scholar
  15. Harris RA (1980) Interaction between narcotic agonists, partial agonists, and antagonists evaluated by schedule controlled behavior. J Pharmacol Exp Ther 213:497–503Google Scholar
  16. Herling S, Woods JH (1981) Discriminative stimulus effects of narcotics: evidence for multiple receptor mediated actions. Life Sci 28:1571–1584Google Scholar
  17. Herling S, Winger GD, Coale EH, Hein DW, Woods JH (1980) Similarity of the discriminative stimulus effects of dextrorphan, ketamine, and cyclazocine in the pigeon. Fed Proc 39:994Google Scholar
  18. Herling S, Solomon RE, Woods JH (1983) Discriminative stimulus effects of dextrorphan in pigeons. J Pharmacol Exp Ther 227:723–731Google Scholar
  19. Holtzman SG (1980) Phencyclidine-like discriminative effects of opioids in the rat. J Pharmacol Exp Ther 214:614–619Google Scholar
  20. Jasinski DR, Martin WR, Mansky PA (1971) Progress report on the assessment of the antagonist nalbuphine and GPA-2087 for abuse potential and studies of the effects of dextromethorphan in man. Reported to the 33rd Meeting, Committee on Problems of Drug Dependence, Toronto, Canada, National Academy of Sciences/National Research Council, Vol. 1, 143–178Google Scholar
  21. Jasinski DR, Martin WR, Sapira JD (1968) Antagonism of the subjective behavioral, pupillary and respiratory depressant effects of cyclazocine by naloxone. Clin Pharmacol Ther 9:215–222Google Scholar
  22. Martin WR, Eades CG, Thompson JA, Huppler RE, Gilbert PE (1976) The effects of morphine- and nalorphine-like drugs in the nondependent and morphine-dependent chronic spinal dog. J Pharmacol Exp Ther 197:517–532Google Scholar
  23. McMillan DE (1969) Behavioral interactions of naloxone with morphine and cyclazocine in the pigeon. Fed Proc 28:736Google Scholar
  24. McMillan DE, Wolf PS, Carchman RA (1970) Antagonism of the behavioral effects of morphine and methadone by narcotic antagonists in the pigeon. J Pharmacol Exp Ther 175:443–458Google Scholar
  25. McNicholas LF, Martin WR (1984) New and experimental therapeutic roles for naloxone and related opioid antagonists. Drugs 27:81–93Google Scholar
  26. Ruffing D, Domino EF (1981) Effects of selected opioid agonists and antagonists on DMT and LSD-25 induced disruption of bar pressing behavior in the rat. Psychopharmacology 75:226–230Google Scholar
  27. Ruffing D, Kovacic B, Demetriou S, Domino EF (1979) Naloxone enhancement of DMT induced suppression of food-rewarded bar pressing behavior in the rat. Psychopharmacology 62:207–210Google Scholar
  28. Shannon HE (1981) Evaluation of phencyclidine analogues on the basis of their discriminative stimulus properties in the rat. J Pharmacol Exp Ther 216:543–553Google Scholar
  29. Shannon HE (1982) Pharmacological analysis of the phencyclidine-like discriminative stimulus properties of narcotic derivatives in rats. J Pharmacol Exp Ther 222:146–151Google Scholar
  30. Teal JJ, Holtzman SG (1980) Stereoselectivity of the stimulus effects of morphine and cyclazocine in the squirrel monkey. J Pharmacol Exp Ther 215:369–376Google Scholar
  31. Vincent JP, Kartalovski B, Geneste P, Kamenka JM, Lazdunski M (1979) Interaction of phencyclidine (“angel dust”) with a specific receptor in rat brain membranes. Proc Natl Acad Sci USA 76:4678–4682Google Scholar
  32. Wagner GC, Masters DB, Tomie A (1984) Effects of phencyclidine, haloperidol, and naloxone on fixed-interval performance in rats. Psychopharmacology 84:32–38Google Scholar
  33. Woods JH (1969) Effects of morphine, methadone and codeine on schedule-controlled behavior in the pigeon. Fed Proc 28:511Google Scholar
  34. Wu KM, Martin WR (1982) Effects of naloxone and fentanyl in acutely decerebrated dog. Life Sci 31:151–157Google Scholar
  35. Zukin SR, Zukin RS (1979) Specific (3H)-phencyclidine binding in rat central nervous system. Proc Natl Acad Sci USA 76:5372–5376Google Scholar
  36. Zukin SR, Zukin RS (1980) (3H)-phencyclidine binding to specific brain receptor sites. Psychopharmacology Bull 16:59–62Google Scholar

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • Tambay Taşkin
    • 1
  1. 1.Pharmacological Research Unit, Drug and Cosmetics Research DivisionRefik Saydam Central Institute of HygieneAnkaraTurkey

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