Opioid antagonist naloxone potentiates anxiogenic-like action of cholecystokinin agonists in elevated plus-maze

Neuropeptides. 1998 Jun;32(3):235-40. doi: 10.1016/s0143-4179(98)90042-7.

Abstract

This study investigated the interplay of cholecystokinin (CCK) and endogenous opioid peptides in the regulation of anxiety. The acute administration of non-selective CCK agonist caerulein (1 and 5 microg/kg) and a selective CCK(B) receptor agonist BOC-CCK-4 (1, 10 and 50 microg/kg) induced a dose-dependent anxiogenic-like action in the plus-maze model of anxiety. BOC-CCK-4 displayed a similar efficacy with caerulein, indicating that the described effect was mediated via CCK(B) receptor subtype. The opioid antagonist naloxone itself (0.5 mg/kg) did not change the exploratory activity of rats in the plus-maze. However, the combination of naloxone with the sub-effective doses of caerulein (1 microg/kg) and BOC-CCK-4 (1 microg/kg) induced a significant inhibition of exploratory behaviour in rats. Accordingly, CCK and endogenous opioid peptides have an antagonistic role in the exploratory model of anxiety in rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / chemically induced*
  • Ceruletide / pharmacology
  • Cholecystokinin / agonists*
  • Disease Models, Animal
  • Drug Synergism
  • Exploratory Behavior / drug effects
  • Male
  • Naloxone / pharmacology*
  • Narcotic Antagonists / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptor, Cholecystokinin B
  • Receptors, Cholecystokinin / agonists
  • Receptors, Cholecystokinin / physiology
  • Tetragastrin / analogs & derivatives
  • Tetragastrin / pharmacology

Substances

  • Narcotic Antagonists
  • Receptor, Cholecystokinin B
  • Receptors, Cholecystokinin
  • Tetragastrin
  • Naloxone
  • butyloxycarbonyl-tryptophyl-methionyl-aspartyl-phenylalaninamide
  • Ceruletide
  • Cholecystokinin