Corticotropin releasing factor and amphetamine exaggerate partial agonist properties of benzodiazepine antagonist Ro 15-1788 in the conflict test.

K T Britton, G Lee, G F Koob
Author Information
  1. K T Britton: Department of Psychiatry, Veterans Administration Medical Center, La Jolla, CA 92161.

Abstract

The central nervous system stimulants corticotropin releasing factor (CRF) and amphetamine were administered in combination with the benzodiazepine ligands Ro 15-1788 and FG 7142 in order to assess their benzodiazepine agonist and antagonist receptor properties in an operant conflict test in rats. Ro 15-1788, which was without behavioral activity in this test when given alone, reversed the suppression of punished responding produced by CRF and amphetamine in a dose-dependent manner. Chlordiazepoxide, which produced a release of punished responding by itself, also reversed the suppression of punished responding produced by CRF but not that of amphetamine. The benzodiazepine inverse agonist FG 7142, in contrast, enhanced the rate suppressing actions of both CRF and amphetamine. In a locomotor activity test, Ro 15-1788 failed to block the locomotor activation observed with CRF and amphetamine. The results suggest that "anxiety" or stress-enhancing compounds may enhance the partial agonist properties of Ro 15-1788 in certain test situations.

References

  1. Science. 1980 Jan 18;207(4428):274-81 [PMID: 6101294]
  2. Nature. 1982 May 27;297(5864):331-3 [PMID: 6978997]
  3. Brain Res. 1984 Sep 17;310(1):154-6 [PMID: 6434155]
  4. Psychopharmacology (Berl). 1986;88(1):1-11 [PMID: 3003778]
  5. Nature. 1981 Apr 9;290(5806):514-6 [PMID: 6261143]
  6. Brain Res. 1983 Nov 14;278(1-2):332-6 [PMID: 6605787]
  7. Psychopharmacology (Berl). 1985;85(4):483-5 [PMID: 3927344]
  8. Psychopharmacology (Berl). 1986;88(2):177-83 [PMID: 3006110]
  9. Lancet. 1983 Jul 9;2(8341):98-9 [PMID: 6134976]
  10. Nature. 1981 Dec 24;294(5843):763-5 [PMID: 6275273]
  11. Eur J Pharmacol. 1983 Jun 3;90(2-3):263-8 [PMID: 6307728]
  12. Psychopharmacology (Berl). 1986;90(2):173-8 [PMID: 3097697]
  13. Life Sci. 1983 Jul 25;33(4):393-9 [PMID: 6308372]
  14. Eur J Pharmacol. 1983 Mar 18;88(1):111-6 [PMID: 6406240]
  15. Psychopharmacology (Berl). 1982;78(1):8-18 [PMID: 6292984]
  16. Psychopharmacology (Berl). 1985;86(1-2):170-4 [PMID: 3927353]
  17. Proc Natl Acad Sci U S A. 1983 Apr;80(7):2072-6 [PMID: 6300891]
  18. Neuropharmacology. 1982 Oct;21(10):1033-7 [PMID: 6815546]
  19. Psychopharmacology (Berl). 1984;83(3):249-56 [PMID: 6089247]
  20. Nature. 1982 Feb 4;295(5848):436-8 [PMID: 6276771]
  21. Life Sci. 1983 May 30;32(22):2579-84 [PMID: 6406779]
  22. Eur J Pharmacol. 1982 Jul 30;81(4):655-8 [PMID: 6811297]
  23. Psychopharmacology (Berl). 1986;88(4):514-9 [PMID: 3085141]
  24. Regul Pept. 1986 Dec 30;16(3-4):315-20 [PMID: 3031744]
  25. Life Sci. 1984 Jun 18;34(25):2525-33 [PMID: 6328168]
  26. J Neurochem. 1981 Sep;37(3):714-22 [PMID: 6268754]
  27. Science. 1980 Jan 18;207(4428):329-31 [PMID: 7188649]

Grants

  1. AA04620/NIAAA NIH HHS

MeSH Term

Amphetamine
Animals
Behavior, Animal
Carbolines
Chlordiazepoxide
Conflict, Psychological
Corticotropin-Releasing Hormone
Drug Interactions
Flumazenil
Male
Motor Activity
Rats
Rats, Inbred Strains

Chemicals

Carbolines
Flumazenil
FG 7142
Chlordiazepoxide
Corticotropin-Releasing Hormone
Amphetamine

Word Cloud

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