Effect of pyroglutamic acid stereoisomers on ECS and scopolamine-induced memory disruption and brain acetylcholine levels in the rat.
The acquisition of a passive avoidance conditioned response was disrupted in the rat by electroconvulsive shock (ECS) and scopolamine administration. D,L-pyroglutamic acid (D,L-PCA) 500 and 1000 mg/kg, administered as arginine salt 120 min before the retest, prevented both the ECS and scopolamine-induced amnesia. Arginine alone was ineffective. Scopolamine brought about a 52 and 39% decrease, respectively, in cortical and hippocampal acetylcholine (ACh) levels, measured by means of a gas-chromatographic method. D,L-PCA 500 and 1000 mg/kg also prevented the decrease in brain ACh level. When the two isomers were studied separately, D-PCA was more effective than L-PCA and antagonized scopolamine-induced amnesia at the doses of 250 and 500 mg/kg. In conclusion, D,L-PCA is active on cortical and hippocampal cholinergic mechanisms and, like other 2-oxopyrrolidone derivatives, shows cognition-enhancing properties.
Spignoli
G
G
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
Magnani
M
M
Giovannini
M G
MG
Pepeu
G
G
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002794:Choline / Q000378:metabolism; D003216:Conditioning, Operant / Q000187:drug effects; D004597:Electroshock; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D011760:Pyrrolidinones / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012601:Scopolamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013237:Stereoisomerism
D011760:Pyrrolidinones; D012601:Scopolamine; D002794:Choline; D000109:Acetylcholine; D011761:Pyrrolidonecarboxylic Acid