Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

A correlative evaluation of cyclazocine, LSD and naloxone on continuous discriminated avoidance in rats

  • 16 Accesses

  • 16 Citations

Abstract

Cyclazocine, a long acting narcotic antagonist, induces disorientation, hyperirritability and hallucinations. In contrast, naloxone is devoid of any psychotomimetic affects. Cyclazocine (2.5 mg/kg) and LSD (1.0 mg/kg) induced strikingly similar behavioural disruptions on well-established discriminated (Sidman) avoidance performance in rats. Cyclazocine and LSD administration resulted in periods of response-inhibition and a subsequent enhancement of response rates. In the presence of the warning signal rats often failed to lever-press and as a consequence received more shocks. Naloxone (30 mg/kg) had little effect on avoidance responding. The effects of cyclazocine and LSD in rats may be mediated through similar mechanisms.

This is a preview of subscription content, log in to check access.

References

  1. Anger, D.: The dependence of inter-response times upon the relative reinforcement of different inter-response times. J. exp. Psychol. 52, 145–161 (1956).

  2. —: The role of temporal discriminations in the reinforcement of Sidman avoidance behavior. J. exp. Anal. Behav. 6, 477–506 (1963).

  3. Appel, J. B.: Effects of LSD on time-based schedules of reinforcement. Psychopharmacologia (Berl.) 21, 174–186 (1971).

  4. Beaton, J. M., Smythies, J. R., Benington, F., Morin, R. D., Clark, L. C., Jr.: Behavioural effects of some 4-substituted amphetamines. Nature (Lond.) 220, 800–801 (1968).

  5. Bradley, R. J., Johnston, V. S.: Behavioural pharmacology of the hallucinogens. In: Origins and mechanisms of hallucinations, pp. 333–344. W. Keup, ed. New York-London: Plenum Press 1970.

  6. Bridger, W. H.: The interaction of stress and hallucinogenic drug action: Implications for a pathophysiological mechanism in schizophrenia. In: Schizophrenia: Current concepts and research, pp. 470–476, D. V. Siva Sankar, Ph.D., ed. P. J. D. Public Ltd. 1968.

  7. Dandiya, P. C., Gupta, B. D., Gupta, M. L., Patni, S. K.: Effects of LSD on open field performance in rats. Psychopharmacologia (Berl.) 15, 333–340 (1969).

  8. Dixon, A. K.: Evidence of catecholamine mediation in the ‘aberrant’ behaviour induced by Lysergic acid diethylamied (LSD) in the rat. Experientia (Basel) 24, 743–747 (1968).

  9. Fink, M., Itil, T. M., Zaks, A., Freedman, A. M.: EEG patterns of cyclazocine, a narcotic antagonist. In: Neurophysiological and behavioural aspects of psychotropic drugs, pp. 62–71. A. Karczmar and W. Koella, edits. Springfield, Ill.: Ch. C. Thomas 1969.

  10. Freedman, A. M.: Psychopharmacological approaches to narcotics addiction. In: Neuropsychopharmacology Proc. 5th Intern. Cong. Coll. Internat. Neuropsychopharmacolicum, pp. 1021–1024, H. Brill, ed. (1967).

  11. Haertzen, C. A.: Subjective effects of narcotic antagonists cyclazocine and nalorphine on the Addiction Research Centre Inventory (ARCI). Psychopharmacologia (Berl.) 18, 366–377 (1970).

  12. Jaffe, J. H., Brill, L.: Cyclazocine, a long acting narcotic antagonist: its voluntary acceptance as a treatment modality by narcotics abusers. Int. J. Addict. 1, 99–123 (1966).

  13. Jasinski, D. R., Martin, W. R., Haertzen, C. A.: The Human Pharmacology and abuse potential of N-Allylnoroxymorphone (Naloxone). J. Pharmacol. exp. Ther. 157, 420–426 (1967).

  14. — —, Sapira, J. D.: Antagonism of the subjective, behavioural, pupillary, and respiratory effects of cyclazocine by naloxone. Clin. Pharmacol. Ther. 9, 115–222 (1968).

  15. — —, Hoeldtke, R. D.: Effects of short- and long-term administration of pentazocine in man. Clin. Pharmacol. Ther. 11, 385–403 (1970).

  16. Karczmar, A. G., Koella, W.: Certain aspects of recent progress in neuropsychopharmacology. In: Neurophysiological and behavioural aspects of psychotropic drugs, pp. xi-xiii. A. Karczmar and W. Koella, edits. Springfield, Ill.: Ch. C. Thomas 1969.

  17. McNemar, Q.: Psychological Statistics, New York-London: Third Edit. John Wiley and Sons 1962.

  18. Martin, W. R., Fraser, H. F., Gorodetzsky, C. W., Rosenberg, D. E.: Studies of the dependence producing potential of the narcotic antagonist 2-cyclopropylmethyl-2′-hydroxy-5,9-dimethyl-6,7-benzomorphan (cyclazocine, Win 20, 740, ARC 11-C-3). J. Pharmacol. exp. Ther. 150, 426–436 (1965).

  19. —, Gorodetzky, C. W., McClane, T. K.: An experimental study in the treatment of narcotic addicts with cyclazocine. Clin. Pharmacol. Ther. 7, 455–465 (1966).

  20. Olds, J.: Hypothalamic substrates of reward. Physiol. Rev. 42, 554–604 (1962).

  21. Schneider, C.: Behavioural effects of some morphine antagonists and hallucinogens in the rat. Nature (Lond.) 220, 586–587 (1968).

  22. Sidman, M.: Avoidance conditioning with brief shock and no exteroceptive warning signal. Science 118, 157–158 (1953).

  23. —: Some properties of the warning stimulus in avoidance behaviour. J. comp. physiol. Psychol. 48, 444–450 (1955).

  24. —: Avoidance behaviour. In: Operant behaviour: Areas of research and application, pp. 448–498, W. K. Honig, ed. New York: Appleton-Century-Crofts 1966.

  25. —: Behavioural pharmacology. In: Readings in behavioural pharmacology, pp. 92–110, Travis et al., ed. New York: Appleton-Century-Crofts 1970.

  26. Smythies, J. R., Johnston, V. S., Bradley, R. J.: Behavioural models of psychosis. Brit. J. Psychiat. 115, 55–68 (1969).

  27. —, Sykes, E. A.: The effect of mescaline upon the conditioned avoidance response in the rat. Psychopharmacologia (Berl.) 6, 163–172 (1964).

  28. Stein, L.: Facilitation of avoidance behaviour by positive brain stimulation. J. comp. physiol. Psychol. 60, 9–19 (1965).

  29. Volavka, J., Zaks, A., Roubicek, J., Fink, M.: Electrographic effects of diacetylmorphine (heroin) and naloxone in man. Neuropharmacology 9, 587–593 (1970).

  30. Webster, C. D., Willinsky, M. D., Herring, B. S., Walters, G. C.: Effects of C-D-tetrahydrocannabinol on temporally spaced responding and discriminated sidman avoidance behaviour in rats. Nature (Lond.) 232, 498–501 (1971).

  31. Wray, S. R., Cowan, A.: The behavioural effects of levallorphan, cyprenorphine (M 285) and amphetamine on repeated Y-maze performance in rats. Psychopharmacologia (Berl.) 21, 257–267 (1971).

  32. — —: The effects of naloxone, chlorpromazine, and haloperidol pretreatment on levallorphan-induced disruption of rats' operant behaviour. Psychopharmacologia (Berl.) 22, 261–270 (1971).

  33. - - Psychotomimetic anticholinesterase: Correlation between animal and clinical findings. (In prep.) (1972).

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Wray, S.R. A correlative evaluation of cyclazocine, LSD and naloxone on continuous discriminated avoidance in rats. Psychopharmacologia 26, 29–43 (1972). https://doi.org/10.1007/BF00421916

Download citation

Key words

  • Cyclazocine
  • LSD
  • Naloxone
  • Response-Excitation
  • Psychotomimetics
  • Discriminative Avoidance Conditioning