Evidence for potentiation by CCK antagonists of the effect of cholecystokinin octapeptide in the elevated plus-maze

Neuropharmacology. 1994 Jun;33(6):729-35. doi: 10.1016/0028-3908(94)90112-0.

Abstract

Systemic treatment with cholecystokinin octapeptide (CCK-8, 2.5-10 micrograms/kg, s.c.), a non-selective CCK agonist, decreased the exploratory activity of mice in an elevated plus-maze. At higher doses (5-10 micrograms/kg) CCK-8 reduced the frequency of rearing, but only 10 micrograms/kg of CCK-8 significantly inhibited the number of line crossings in the open-field test. A preferential CCKB antagonist L-365,260 (1 and 100 micrograms/kg, i.p.) and a non-selective CCK antagonist proglumide (0.1-1 microgram/kg, i.p.) potentiated the anti-exploratory effect of CCK-8 (2.5 micrograms/kg). Devazepide, a preferential CCKA antagonist, only at a high dose (100 micrograms/kg) tended to increase the action of CCK-8 in the plus-maze. However, the concomitant treatment of CCK-8 with L-365,260 and proglumide, differently from devazepide, also suppressed the locomotor activity in the open-field test. Therefore, it is likely that the potentiation by CCK antagonists of the anti-exploratory effect of CCK-8 is related to the suppression of motor activity. This peculiar interaction between CCK-8 and CCK antagonists could be explained in the light of the opposite role of CCKA and CCKB receptors in the regulation of motor activity in mice.

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Benzodiazepinones / pharmacology
  • Cholecystokinin / antagonists & inhibitors*
  • Devazepide
  • Drug Synergism
  • Exploratory Behavior / drug effects*
  • Female
  • Mice
  • Motor Activity / drug effects
  • Phenylurea Compounds*
  • Proglumide / pharmacology
  • Receptors, Cholecystokinin / antagonists & inhibitors
  • Sincalide / pharmacology*

Substances

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