Abstract
The effect of neuropeptide cholecystokinin (CCK) receptor agonists and antagonists was examined in the rat elevated X-maze model of anxiety. The selective CCK-B receptor antagonists CI-988 (PD 134308) and L-365,260 produced anxiolytic-like effects, whereas MK-329, a CCK-A receptor antagonist, was respectively less potent by factors of 313 and 200. The intracerebroventricular administration of the nonselective CCK receptor agonist caerulein or the selective CCK-B receptor agonist pentagastrin increased dose dependently the level of anxiety. CI-988 dose dependently antagonized the anxiogenic response to pentagastrin but not that induced by pentylenetetrazol. These results strongly suggest that activation of the brain CCK-B receptor induces anxiety and that selective antagonists of this receptor represent a separate class of anxiolytic agents.
MeSH terms
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Animals
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Anxiety*
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Benzodiazepinones / administration & dosage
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Benzodiazepinones / pharmacology*
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Cerebral Ventricles / drug effects
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Cerebral Ventricles / physiology*
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Ceruletide / pharmacology
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Chlordiazepoxide / administration & dosage
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Chlordiazepoxide / pharmacology*
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Cholecystokinin / antagonists & inhibitors*
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Devazepide
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Indoles / administration & dosage
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Indoles / pharmacology*
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Injections, Intraventricular
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Male
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Meglumine / administration & dosage
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Meglumine / analogs & derivatives*
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Meglumine / pharmacology
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Pentagastrin / pharmacology
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Phenylurea Compounds*
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Rats
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Rats, Inbred Strains
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Receptors, Cholecystokinin / drug effects
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Receptors, Cholecystokinin / physiology*
Substances
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Benzodiazepinones
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Indoles
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Phenylurea Compounds
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Receptors, Cholecystokinin
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PD 134308
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L 365260
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Meglumine
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Chlordiazepoxide
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Ceruletide
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Cholecystokinin
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Pentagastrin
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Devazepide