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Benzodiazepine/cholecystokinin interactions at functional CCK receptors in rat brain

1994; Wiley; Volume: 112; Issue: 2 Linguagem: Inglês

10.1111/j.1476-5381.1994.tb13090.x

1476-5381

P. Boden, G.N. Woodruff,

Hypothalamic control of reproductive hormones

The effects of benzodiazepines on cholecystokinin (CCK) responses produced following activation of CCK B receptors by pentagastrin in the ventromedial hypothalamus (VMH) or CCK A receptors by CCK‐8S in the dorsal raphe of the rat brain in vitro have been investigated. The benzodiazepine agonist, flurazepam, at high concentrations, blocked pentagastrin‐induced excitations in the rat VMH yielding an equilibrium constant ( K e ) value of 12.5 μ m . In the rat dorsal raphe, where activation of CCK A receptors leads to neuronal depolarization, flurazepam also produced a weak block of the CCK response. Flurazepam blocked CCK responses but not carbachol‐induced excitations of VMH neurones. The inhibition of CCK responses by flurazepam was not blocked by the benzodiazepine antagonist, flumazenil. These data suggest that flurazepam is a weak antagonist at central CCK B receptors. At central CCK A receptors, flurazepam blocked CCK‐8S responses but the inhibition was not competitive, with a reduction in the peak CCK‐8S obtainable in the presence of flurazepam. These results suggest that flurazepam acts at a site other than the CCK A receptor itself to block CCK responses in the dorsal raphe.