The effects of CCKA and CCKB antagonists on activity in the black/white exploration model of anxiety in mice

Physiol Behav. 1993 Oct;54(4):689-93. doi: 10.1016/0031-9384(93)90077-s.

Abstract

In view of evidence suggesting that cholecystokinin (CCK) may have a role in the mediation of human panic disorders, it was predicted that CCK receptor antagonists may have anxiolytic-like activity in an animal model of anxiety, the black/white exploration test. Data revealed that, in mice, the CCKA receptor antagonist, devazepide (formerly L-364,718, MK-329), produced a clear anxiolytic-like profile with an inverted U-shaped dose-response curve centered around 5 micrograms/kg. Similarly, L-365,031, a specific, but less potent, CCKA antagonist, also produced a profile consistent with weak anxiolysis but only at 5 micrograms/kg. By direct contrast, the potent and specific CCKB antagonist L-365,260 had no robust anxiolytic-like effects in this test. Therefore, these data suggest that devazepide has the greatest effects in this model, that L-365,031 is only marginally active, and that L-365,260 is without influence. These results suggest that CCKA receptor mechanisms are involved in the mediation of anxiolytic-like effects in the black/white model of exploration in mice.

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology
  • Anxiety / psychology*
  • Benzodiazepinones / pharmacology
  • Cholecystokinin / antagonists & inhibitors
  • Devazepide
  • Dose-Response Relationship, Drug
  • Exploratory Behavior / drug effects*
  • Male
  • Mice
  • Mice, Inbred DBA
  • Phenylurea Compounds*
  • Receptors, Cholecystokinin / antagonists & inhibitors*

Substances

  • Anti-Anxiety Agents
  • Benzodiazepinones
  • Phenylurea Compounds
  • Receptors, Cholecystokinin
  • L 365031
  • L 365260
  • Cholecystokinin
  • Devazepide