Benzodiazepines antagonize cholecystokinin-induced activation of rat hippocampal neurones

Abstract

Cholecystokinin (CCK) is a neuropeptide present in the mammalian CSN. In all species studied, the highest concentrations of this neuropeptide was found in the cerebral cortex, the amygdala and the hippocampus. Five molecular forms of CCK having 39, 33, 13, 8 and 4 amino acid residues have been identified in the CNS, the sulfated octapeptide (CCK8) being the most abundant form detected. Specific CCK binding sites have been demonstrated in the rat, guinea pig and human brain. CCK8, applied by microiontophoresis to deep cortical neurons and hippocampal pyramidal neurons [in rats], has a powerful excitatory effect, whereas the non-sulfated CCK octapeptide has no such effect on these neurons. Low doses of benzodiazepines depress the spontaneous activity of hippocampal pyramidal neurons. Benzodiazepines at very low doses antagonize selectively the CCK8-induced activation of rat hippocampal pyramidal neurons. This antagonistic action might be involved in the anxiolytic effect of these drugs.