Psychopharmacology

, Volume 88, Issue 4, pp 445–450 | Cite as

The shock probe conflict procedure. A new assay responsive to benzodiazepines, barbiturates and related compounds

  • Theo F. Meert
  • Francis C. Colpaert
Original Investigations

Abstract

Rats that are placed in a novel environment containing a probe will explore the environment and the probe. Exploration of the probe is reduced when the probe is electrified. We here report that chlordiazepoxide blocks this inhibition, and have determined some of the pharmacological features of this new experimental procedure. The procedure appears to be sensitive to the effects of several benzodiazepines, barbiturates, and related compounds. Limited activity was observed with most 5-HT antagonists, ritanserin, an anticholinergic, a β-adrenergic blocker and a neuroleptic. Of the antidepressants, only imipramine had some limited activity. Inactive compounds in this procedure include benzodiazepine antagonists, buspirone, convulsants, opiates, an opiate antagonist, stimulants, a putative DA agonist and antagonist, histamine antagonists, a cholinomimetic, anticholinergics, a NE antagonist, α2 agonists, an α2 antagonist, MAO inhibitors, 5-HTP and LSD.

Key words

Conflict test Anxiolytics Benzodiazepines Barbiturates 5-HT-antagonists Ritanserin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aron C, Simon P, Larousse C, Boissier JR (1971) Evaluation of a rapid technique for detecting minor tranquillizers. Neuropharmacology 10:459–469Google Scholar
  2. Boissier JR, Simon P, Aron C (1968) A new method for rapid screening of minor tranquillizers in mice. Eur J Pharmacol 4:145–151Google Scholar
  3. Colpaert FC, Meert TF, Niemegeers CJE, Janssen PAJ (1985) Ritanserin: A pure and selective antagonist of LSD discrimination in rat. Psychopharmacology 86:45–54Google Scholar
  4. Cook L, Davidson AB (1973) Effects of behaviorally active drugs in a conflict-punishment procedure in rats. In: Garattini S, Mussini E, Randall O (eds) The benzodiazepines, Raven Press, New York, p 327–345Google Scholar
  5. Cooper SJ (1982) Effects of opiate antagonists and of morphine on chlordiazepoxide-induced hyperdipsia in the water-deprived rats. Neuropharmacology 21:1013–1017Google Scholar
  6. Crawley JN (1985) Exploratory behavior models of anxiety in mice. Neurosci Biobehav Rev 9:37–44Google Scholar
  7. File SE (1980) The use of the social interaction as a method for detecting anxiolytic activity of chlordiazepoxide-like drugs. J Neurosci Methods 2:219–238Google Scholar
  8. File SE (1981) Behavioural effects of serotonin depletion. In: Rose FC (ed) Metabolic disorders of the nervous system, Pitman, pp 429–445Google Scholar
  9. File SE (1982) Development and retention of tolerance to the sedative effects of chlordiazepoxide: role of apparatus cues. Eur J Pharmacol 81:637–643Google Scholar
  10. File SE (1985) What can be learned from the effects of benzodiazepines on exploratory behavior? Neurosci Biobehav Rev 9:45–54Google Scholar
  11. Finney DJ (1964) Statistical Methods in Biological Assay. 2nd Ed., Hafner, New YorkGoogle Scholar
  12. Geller I, Blum K (1970) The effects of 5-HTP on parachlorophenylalanine (p-cPA) attenuation of “conflict” behavior. Eur J Pharmacol 9:319–324Google Scholar
  13. Geller I, Hartmann RJ, Croy DJ (1974) Attenuation of conflict behavior with cinanserin, a serotonin antagonist: Reversal of the effect with 5-hydroxytryptophan and α-methyltryptamine. Res Commun Chem Pathol Pharmacol 7:165–174Google Scholar
  14. Geller I, Seifter J (1960) The effects of meprobamate, barbiturates, d-amphetamine and promazine on experimentally induced conflict in the rat. Psychopharmacologia 1:482–492Google Scholar
  15. Goldberg ME, Salama AI, Patel JB, Malick JB (1983) Novel non-benzodiazepine anxiolytics. Neuropharmacology 22:1499–1504Google Scholar
  16. Graeff FG, Schoenfeld RI (1970) Tryptaminergic mechanisms in punished and nonpunished behavior. J Pharmacol Exp Ther 173:277–283Google Scholar
  17. Gray JA (1981) Anxiety as a paradigm case of emotion. Br Med Bull 37:193–197Google Scholar
  18. Iversen SD (1980) Animal models of anxiety and benzodiazepine actions. Arzneimittelforsch 30:862–868Google Scholar
  19. Kandell ER (1983) From metapsychology to molecular biology. Explorations into the nature of anxiety. Am J Psychiatry 140:1277–1293Google Scholar
  20. Kilts CD, Commissaris RL, Rech RH (1981) Comparison of anti-conflict drug effects in three experimental animal models of anxiety. Psychopharmacology 74:290–296Google Scholar
  21. Lippa AS, Coupet J, Greenblatt EN, Klepner CA, Beer B (1979) A synthetic non-benzodiazepine ligand for benzodiazepine receptors: A probe for investigating neural substrates of anxiety. Pharmacol Biochem Behav 11:99–106Google Scholar
  22. Marriott SA, Smith EF (1972) An analysis of drug effects in mice exposed to a simple novel environment. Psychopharmacologia 24:397–406Google Scholar
  23. McCown TJ, Vogel RA, Breese GR (1983) An efficient chronic conflict paradigm: lick suppression by incremental footshock. Pharmacol Biochem Behav 18:277–279Google Scholar
  24. McMillen BA, Mattrace LA (1983) Comparative neuropharmacology of buspirone and MJ-13805, a potential anti-axiety drug. J Neural Transm 57:255–265Google Scholar
  25. Petersen EN, Lassen JB (1981) A water lick conflict paradigm using drug experienced rats. Psychopharmacologia 75:236–239Google Scholar
  26. Riblet LA, Eison AS, Eison MS, Newton RE, Taylor DP, Temple DL (1983) Buspirone: An anxioselective alternative for the management of anxiety disorders. Prog Neuropsychopharmacol Psychiatry 7:663–668Google Scholar
  27. Robichaud RC, Sledge KL (1969) The effects of p-chlorophenylalanine on experimentally induced conflict in the rat. Life Sci 8:965–969Google Scholar
  28. Sepinwall J, Cook L (1978) Behavioral pharmacology of antianxiety drugs. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of Psychopharmacology, Volume 13. Biology of mood and antianxiety drugs, Plenum Press, New York, pp 345–393Google Scholar
  29. Sepinwall J, Grodsky FC, Cook L (1978) Conflict behavior in the squirrel monkey: Effects of chlordiazepoxide, diazepam and N-desmethyldiazepam. J Pharmacol Exp Ther 204:88–102Google Scholar
  30. Siegel S (1956) Nonparametric statistics for behavioral sciences. McGraw-Hill Book Company, New YorkGoogle Scholar
  31. Soubrié P, Kulkarni S, Simon P, Boissier JR (1975) Effects des anxiolytiques sur la prise de nouriture de rats et de souris placés en situation nouvelle ou familière. Psychopharmacologia 45:203–210MathSciNetMATHGoogle Scholar
  32. Stein L, Wise CD, Berger BD (1973) Antianxiety action of benzodiazepines: Decrease in activity of serotonin neurons in the punishment system. In: Garrattini S, Mussini E, Randall O (eds) The benzodiazepines, Raven Press, New York, pp 299–326Google Scholar
  33. Taylor DP, Riblet LA, Stanton HC, Eison AS, Eison MS, Temple DL (1982) Dopamine and antianxiety activity. Pharmacol Biochem Behav 17, Suppl. 1:25–35Google Scholar
  34. Treit D (1985) Animal models for the study of anti-anxiety agents: A review. Neurosci Biobehav Rev 9:203–222Google Scholar
  35. Ts'O TO, Chenoweth MB (1976) Comparison between chronic chlordiazepoxide treatment and shock removal in a conflict situation in rats. Neuropharmacology 15:99–101Google Scholar
  36. Vogel JR, Beer B, Clody DE (1971) A simple and reliable conflict procedure for testing anti-anxiety agents. Psychopharmacologia 21:1–7Google Scholar
  37. Vogel RA, Frye GD, Wilson JH, Kuhn CM, Koepke KM, Mailman RB, Mueller RA, Breese GR (1980) Attenuation of the effects of punishment by ethanol: comparisons with chlordiazepoxide. Psychopharmacologia 71:123–129Google Scholar

Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • Theo F. Meert
    • 1
  • Francis C. Colpaert
    • 1
  1. 1.Department of PsychopharmacologyJanssen Pharmaceutica Research LaboratoriesBeerseBelgium

Personalised recommendations