Attenuation of CCK-induced aversion in rats on the elevated x-maze by the selective 5-HT1A receptor antagonists (+) WAY100135 and WAY100635

Neuropharmacology. 1995 Jul;34(7):805-11. doi: 10.1016/0028-3908(95)00037-7.

Abstract

The present study determined the effect of pretreatment with "silent" selective 5-HT1A receptor antagonists on cholecystokinin (CCK)-mediated effects on rat behaviour in the elevated x-maze model of anxiety. In the absence of 5-HT1A receptor antagonists, non-sulphated cholecystokinin-octapeptide (CCK-8ns; 10 and 50 micrograms/kg, i.p.; 30 min prior to testing) produced an anxiogenic profile of behaviour on the x-maze, reducing the number of open arm entries and the number of exploratory head dips, while increasing the level of risk-assessment as measured by the number of stretched-attend postures. CCK-8ns did not, however, alter ambulatory activity. Two 5-HT1A receptor antagonists were employed in these experiments: (+)WAY100135 (the active enantiomer of N-tert-butyl-3-(4-(2-methoxyphenyl)piperzin-1-yl)- 2-phenylpropronamine) [sequence: see text] and WAY100635 (N-[2-[4(2-methoxyphenyl)-1-piperazinyl-1-piperazinyl]-N-2- pyridinyl)cyclohexanecarbonate [sequence: see text] trihydrochloride). When administered 10 min prior to CCK-8ns, (+) WAY100135 and 0.3 mg/kg s.c.) significantly attenuated profile of CCK-8ns. (+)WAY100135 was also demonstrated to significantly inhibit postsynaptic 5-HT1A receptor-mediated 8-OH-DPAT (8-hydroxy-2-(di-N-propylamino)tetralin)-induced 5-HT syndrome at the same dose used in the x-maze experiment. Neither (+)WAY100135 nor WAY100635 had any affects on ambulatory activity. These results support a CCK/5-HT1A receptor interaction in the modulation of aversion in rats exposed to the elevated x-maze.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Anxiety
  • Behavior, Animal
  • Cholecystokinin / pharmacology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Male
  • Maze Learning / drug effects*
  • Peptide Fragments / pharmacology
  • Piperazines / pharmacology*
  • Pyridines / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Serotonin Antagonists / pharmacology*
  • Sincalide / pharmacology*
  • Time Factors

Substances

  • Peptide Fragments
  • Piperazines
  • Pyridines
  • Serotonin Antagonists
  • WAY 100135
  • cholecystokinin 10 C-terminal fragment
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Cholecystokinin
  • Sincalide