Cholecystokinin-related peptides, after systemic or central administration, prevent carbon monoxide-induced amnesia in mice

T. Maurice, M. Hiramatsu, T. Kameyama, T. Hasegawa, Toshitaka Nabeshima

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Abstract

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 μg/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°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 μg/mouse) and CCK-8S (0.03-1 μg/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 μg/kg s.c. or 10 μg/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. The effect of centrally administered ceruletide was blocked selectively and completely by L-365,260 (1-10 mg/kg i.p.). These results indicate that CCK peptides have neuroprotective properties in CO-induced amnesia, a condition which may involve glutamate excitotoxicity. Two different mechanisms appeared to be responsible for the protective action of ceruletide, a systemic mechanism, operating through CCK-A receptors, and a centrally acting mechanism, operating through CCK-B receptors.

Original languageEnglish
Pages (from-to)665-673
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume269
Issue number2
Publication statusPublished - 01-01-1994
Externally publishedYes

Fingerprint

Amnesia
Ceruletide
Cholecystokinin
Carbon Monoxide
Peptides
Cholecystokinin A Receptor
Dizocilpine Maleate
Devazepide
Tetragastrin
Cholecystokinin B Receptor
Imines
Body Temperature
Short-Term Memory
Glutamic Acid
Gases

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

@article{dea6f03302934c929141948a5c30710a,
title = "Cholecystokinin-related peptides, after systemic or central administration, prevent carbon monoxide-induced amnesia in mice",
abstract = "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 μg/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°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 μg/mouse) and CCK-8S (0.03-1 μg/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 μg/kg s.c. or 10 μg/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. The effect of centrally administered ceruletide was blocked selectively and completely by L-365,260 (1-10 mg/kg i.p.). These results indicate that CCK peptides have neuroprotective properties in CO-induced amnesia, a condition which may involve glutamate excitotoxicity. Two different mechanisms appeared to be responsible for the protective action of ceruletide, a systemic mechanism, operating through CCK-A receptors, and a centrally acting mechanism, operating through CCK-B receptors.",
author = "T. Maurice and M. Hiramatsu and T. Kameyama and T. Hasegawa and Toshitaka Nabeshima",
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Cholecystokinin-related peptides, after systemic or central administration, prevent carbon monoxide-induced amnesia in mice. / Maurice, T.; Hiramatsu, M.; Kameyama, T.; Hasegawa, T.; Nabeshima, Toshitaka.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 269, No. 2, 01.01.1994, p. 665-673.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Cholecystokinin-related peptides, after systemic or central administration, prevent carbon monoxide-induced amnesia in mice

AU - Maurice, T.

AU - Hiramatsu, M.

AU - Kameyama, T.

AU - Hasegawa, T.

AU - Nabeshima, Toshitaka

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Y1 - 1994/1/1

N2 - 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 μg/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°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 μg/mouse) and CCK-8S (0.03-1 μg/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 μg/kg s.c. or 10 μg/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. The effect of centrally administered ceruletide was blocked selectively and completely by L-365,260 (1-10 mg/kg i.p.). These results indicate that CCK peptides have neuroprotective properties in CO-induced amnesia, a condition which may involve glutamate excitotoxicity. Two different mechanisms appeared to be responsible for the protective action of ceruletide, a systemic mechanism, operating through CCK-A receptors, and a centrally acting mechanism, operating through CCK-B receptors.

AB - 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 μg/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°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 μg/mouse) and CCK-8S (0.03-1 μg/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 μg/kg s.c. or 10 μg/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. The effect of centrally administered ceruletide was blocked selectively and completely by L-365,260 (1-10 mg/kg i.p.). These results indicate that CCK peptides have neuroprotective properties in CO-induced amnesia, a condition which may involve glutamate excitotoxicity. Two different mechanisms appeared to be responsible for the protective action of ceruletide, a systemic mechanism, operating through CCK-A receptors, and a centrally acting mechanism, operating through CCK-B receptors.

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