TY - JOUR
T1 - Effects of DM-9384, a cyclic derivative of GABA, on amnesia and decreases in GABA(A) and muscarinic receptors induced by cycloheximide
AU - Nabeshima, T.
AU - Tohyama, K.
AU - Murase, K.
AU - Ishihara, S.
AU - Kameyama, T.
AU - Yamasaki, T.
AU - Hatanaka, S.
AU - Kojima, H.
AU - Sakurai, T.
AU - Takasu, Y.
AU - Shiotani, T.
PY - 1991
Y1 - 1991
N2 - The effects of N-(2,6-dimethyl-phenyl)-2-(2-oxo-1-pyrrolidinyl)-acetamide [DM-9384], a cyclic derivative of GABA, were investigated in the cycloheximide (CXM)-induced amnesia animal model using the passive avoidance task. Pre- and post-training and pre-retention test administration of DM-9384 attenuated the CXM-induced amnesia as indicated by prolongation of step-down latency. Aniracetam, another cyclic derivative of GABA, also showed antiamnesic effects. Scopolamine, a muscarinic ACh receptor antagonist, and the GABA antagonists, picrotoxin and bicuculline, all antagonized the antiamnesic effects of DM-9384. CXM decreased the number of GABA(A) and muscarinic ACh receptor binding sites. DM-9384 not only inhibited this effect but actually increased the latter. These results suggest that DM-9384 attenuates CXM-induced amnesia by interacting with GABAergic and AChergic neuronal systems and enhancing protein synthesis in the brain.
AB - The effects of N-(2,6-dimethyl-phenyl)-2-(2-oxo-1-pyrrolidinyl)-acetamide [DM-9384], a cyclic derivative of GABA, were investigated in the cycloheximide (CXM)-induced amnesia animal model using the passive avoidance task. Pre- and post-training and pre-retention test administration of DM-9384 attenuated the CXM-induced amnesia as indicated by prolongation of step-down latency. Aniracetam, another cyclic derivative of GABA, also showed antiamnesic effects. Scopolamine, a muscarinic ACh receptor antagonist, and the GABA antagonists, picrotoxin and bicuculline, all antagonized the antiamnesic effects of DM-9384. CXM decreased the number of GABA(A) and muscarinic ACh receptor binding sites. DM-9384 not only inhibited this effect but actually increased the latter. These results suggest that DM-9384 attenuates CXM-induced amnesia by interacting with GABAergic and AChergic neuronal systems and enhancing protein synthesis in the brain.
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M3 - Article
C2 - 1850466
AN - SCOPUS:0025954345
SN - 0022-3565
VL - 257
SP - 271
EP - 275
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 1
ER -