sincalide and Amnesia

The neuroprotective actions of cholecystokinin (CCK) peptides were investigated in a mouse hypoxia model, in which the animals were successively exposed to CO gas. Working memory impairment 5 days after CO exposure was examined by using a Y-maze test; delayed amnesia was examined 7 days after CO exposure, by using a step-down type passive avoidance test. Ceruletide (1-100 micrograms/kg, given s.c. 30 min before CO exposure) significantly prevented the CO-induced impairment of performance in both tests, the improvement being correlated with the severity of hypoxia. This severity was increased by maintaining the body temperature at 38 degrees C. Ceruletide was less effective when injected immediately after a single CO exposure. The order of potency of the CCK-peptides administered systemically was: ceruletide > CCK-8S > CCK-8NS >> CCK-4. Ceruletide (0.03-0.3 micrograms/mouse) and CCK-8S (0.03-1 microgram/mouse) prevented CO-induced amnesia after i.c.v. administration. Under all experimental conditions, dizocilpine [MK-801, (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate, 500 micrograms/kg s.c. or 10 micrograms/mouse i.c.v.] prevented completely the CO-induced amnesia. The protective effects of systemic ceruletide were blocked, partially but significantly, by the preadministration of L-364,718 (3S-(-)-N-[2,3-dihydro-1-methyl-2-oxo-S-phenyl-1H-1,4- benzodiazepine-3-yl]-1H-indole-2-carboxamide, 1-10 mg/kg i.p.), a selective CCK-A receptor antagonist. L-365,260 ([3R-(+)-2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3-yl] -N' - [3-methyl-phenyl]urea), a CCK-B antagonist, also decreased ceruletide-induced protection.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amnesia; Animals; Avoidance Learning; Carbon Monoxide; Ceruletide; Disease Models, Animal; Injections, Intraventricular; Male; Mice; Sincalide

The effects of several doses of intracerebroventricularly injected cholecystokinin octapeptide sulfate ester (CCK-8-SE) and nonsulfated scholecystokinin octapeptide (CCK-8-NS) were studied on electroconvulsive shock (ECS)-induced retrograde amnesia, as measured in a one-trial step-through passive avoidance paradigm. Both CCK-8-SE and CCK-8-NS were able to attenuate amnesia slightly when they were injected into rats 10 min prior to ECS treatment, possibly by reducing the severity of the ECS-induced seizures. Of the treatments carried out immediately after ECS, only the 0.8 pmole dose of CCK-8-NS could significantly restore retrograde amnesia. After treatment 20 min prior to testing 24-hr retention, no effect of the peptides was observed. The lack of a dose-dependency and of any effect on retrieval raises the possibility that the CCK octapeptides influence memory processes by an indirect mechanism.

Topics: Amnesia; Amnesia, Retrograde; Animals; Electroshock; Humans; Injections, Intraventricular; Male; Rats; Sincalide; Structure-Activity Relationship; Sulfates