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Antiamnesic effects of magnesium pyrrolidone carboxylate (MAG 2) in three models of amnesia in the mouse

Roger D. Porsolt, Antoine Lenègre, I Avril, P. Parot, Gilles Tran

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Abstract

Abstract The effects of magnesium pyrrolidone carboxylate (MAG 2) on the amnesias induced by scopolamine, diazepam, and electroconvulsive shock (ECS) were studied in a passive avoidance procedure in the mouse and compared with the effects of a standard dose of piracetam. Amnesia was induced by injecting scopolamine or diazepam (1 mg/kg intraperitoneally [i.p.]) 30 min before or ECS administered immediately after the first session (S1) of the passive avoidance task. MAG 2 was studied in a dose range of 128 to 1,024 mg/kg and compared with piracetam (2,048 mg/kg), both drugs being administered orally (p.o.) 60 min before S1. Retention was measured 24 hr later (S2) in the absence of any treatment. Further experiments investigated the effects of repeated administration of MAG 2 (twice daily for 3 days) on diazepam‐induced amnesia. Additional experiments investigated the interactions of the compound with the major behavioral effects of the amnesic treatments, namely scopolamine‐induced hyperactivity, diazepam‐induced release of punished behavior (four plates test), and ECS‐induced convulsions. MAG 2 dose‐dependently attenuated the memory deficits induced by the three amnesic treatments after acute treatment and more effectively antagonized diazepam‐induced amnesia after repeated than after acute treatment. It did not affect either scopolamine‐induced hyperactivity, diazepam‐induced release of punished behavior or ECS‐induced convulsions. These results point to the specificity of MAG 2′s antiamnesic activity and suggest that it might be a useful agent for the treatment of memory deficits of different origins in man.

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Abstract The effects of magnesium pyrrolidone carboxylate (MAG 2) on the amnesias induced by scopolamine, diazepam, and electroconvulsive shock (ECS) were studied in a passive avoidance procedure in the mouse and compared with the effects of a standard dose of piracetam. Amnesia was induced by injecting scopolamine or diazepam (1 mg/kg intraperitoneally [i.p.]) 30 min before or ECS administered immediately after the first session (S1) of the passive avoidance task. MAG 2 was studied in a dose range of 128 to 1,024 mg/kg and compared with piracetam (2,048 mg/kg), both drugs being administered orally (p.o.) 60 min before S1. Retention was measured 24 hr later (S2) in the absence of any treatment. Further experiments investigated the effects of repeated administration of MAG 2 (twice daily for 3 days) on diazepam‐induced amnesia. Additional experiments investigated the interactions of the compound with the major behavioral effects of the amnesic treatments, namely scopolamine‐induced hyperactivity, diazepam‐induced release of punished behavior (four plates test), and ECS‐induced convulsions. MAG 2 dose‐dependently attenuated the memory deficits induced by the three amnesic treatments after acute treatment and more effectively antagonized diazepam‐induced amnesia after repeated than after acute treatment. It did not affect either scopolamine‐induced hyperactivity, diazepam‐induced release of punished behavior or ECS‐induced convulsions. These results point to the specificity of MAG 2′s antiamnesic activity and suggest that it might be a useful agent for the treatment of memory deficits of different origins in man.

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Available abstract

Abstract The effects of magnesium pyrrolidone carboxylate (MAG 2) on the amnesias induced by scopolamine, diazepam, and electroconvulsive shock (ECS) were studied in a passive avoidance procedure in the mouse and compared with the effects of a standard dose of piracetam. Amnesia was induced by injecting scopolamine or diazepam (1 mg/kg intraperitoneally [i.p.]) 30 min before or ECS administered immediately after the first session (S1) of the passive avoidance task. MAG 2 was studied in a dose range of 128 to 1,024 mg/kg and compared with piracetam (2,048 mg/kg), both drugs being administered orally (p.o.) 60 min before S1. Retention was measured 24 hr later (S2) in the absence of any treatment. Further experiments investigated the effects of repeated administration of MAG 2 (twice daily for 3 days) on diazepam‐induced amnesia. Additional experiments investigated the interactions of the compound with the major behavioral effects of the amnesic treatments, namely scopolamine‐induced hyperactivity, diazepam‐induced release of punished behavior (four plates test), and ECS‐induced convulsions. MAG 2 dose‐dependently attenuated the memory deficits induced by the three amnesic treatments after acute treatment and more effectively antagonized diazepam‐induced amnesia after repeated than after acute treatment. It did not affect either scopolamine‐induced hyperactivity, diazepam‐induced release of punished behavior or ECS‐induced convulsions. These results point to the specificity of MAG 2′s antiamnesic activity and suggest that it might be a useful agent for the treatment of memory deficits of different origins in man.

Key concepts: Amnesia, Diazepam, Piracetam, Convulsion, Retrograde amnesia, Pharmacology, Scopolamine, Chemistry

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