ATTENUATION OF CCK-INDUCED AVERSION IN RATS ON THE ELEVATED X-MAZE BY THE SELECTIVE 5-HT1A RECEPTOR ANTAGONISTS (+)WAY100135 AND WAY100635

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 ana 50 mu g/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-phenylpropronamide) and WAY100635 (N-[2-[4(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinyl)cyclohexanecarbonate trihydrochloride). When administered 10 min prior to CCK-8ns, (+)WAY100135 (1.0 mg/kg s.c.) or WAY100635 (0.03 and 0.3 mg/kg s.c.) significantly attenuated the anxiogenic 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 effects 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.