EFFECTS OF BOC-CCK-4 AND L365.260 ON CORTICAL 5-HT RELEASE IN GUINEA-PIGS ON EXPOSURE TO THE ELEVATED PLUS-MAZE

The elevated plus maze is a well-established model of anxiety, with previous results showing that guinea-pigs handled daily from birth exhibit behaviour in this test similar to rats. In the present microdialysis study exposure of the guinea-pig to the elevated plus maze increased extracellular 5-HT in the lateral prefrontal cortex. The CCK-B receptor agonist BOC-CCK-4 (10 mu g/kg) produced 'anxious' behaviour and potentiated the rise in 5-HT observed on exposure to the X-maze. The basal release of cortical extracellular 5-HT was not affected by BOC-CCK-4. Pretreatment with the selective CCK-B antagonist L365.260 (100 mu g/kg) antagonized both the 'anxious' behaviour and the neurochemical changes induced by BOC-CCK-4 while L365.260 alone produced 'anxiolytic' behaviour, decreased basal extracellular 5-HT and prevented the increase in extracellular 5-HT seen when the guinea-pigs were exposed to the X-maze. Our results show that CCK-B receptor stimulation and blockade induce changes in central extracellular 5-HT levels associated with 'anxious' and 'anxiolytic' behaviour, respectively.