Effects of BOC-CCK-4 and L 365.260 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 micrograms/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 L 365.260 (100 micrograms/kg) antagonized both the 'anxious' behaviour and the neurochemical changes induced by BOC-CCK-4 while L 365.260 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.
Rex
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Institute of Pharmacology and Toxicology, Humboldt University of Berlin, Germany.
Fink
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Marsden
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CA
D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D001570:Benzodiazepinones / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006168:Guinea Pigs; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D017551:Microdialysis; D010671:Phenylurea Compounds; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D011949:Receptors, Cholecystokinin / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism*; D013758:Tetragastrin / Q000031:analogs & derivatives* / Q000494:pharmacology
D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D011949:Receptors, Cholecystokinin; D013758:Tetragastrin; D012701:Serotonin; C058121:L 365260; C063051:butyloxycarbonyl-tryptophyl-methionyl-aspartyl-phenylalaninamide; D006897:Hydroxyindoleacetic Acid