PMID- 7865174
OWN - NLM
STAT- MEDLINE
DCOM- 19950330
LR  - 20191210
VI  - 95
IP  - 3
DP  - 1994
TI  - Effects of nefiracetam on deficits in active avoidance response and hippocampal 
      cholinergic and monoaminergic dysfunctions induced by AF64A in mice.
PG  - 179-93
AB  - The effects of nefiracetam [DM-9384; 
      N-(2,6-dimethyl-phenyl)-2-(2-oxo-pyrrolidinyl)acetamide] and of 
      phosphatidylcholine on a step-up active avoidance response, locomotor activities 
      and regional brain cholinergic and monoaminergic neurotransmitters in 
      AF64A-treated mice were investigated. Intracerebroventricular (i.c.v.) injection 
      of AF64A (ethylcholine mustard aziridinium ion; 8 nmol/ventricle) impaired 
      acquisition and retention of the avoidance task, and increased vertical and 
      horizontal locomotor activities. Regional levels of acetylcholine, noradrenaline, 
      3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxytryptamine (5-HT) and 
      5-hydroxyindoleacetic acid (5-HIAA) were significantly decreased and homovanillic 
      acid (HVA) levels were increased in the hippocampus but not in the septum, 
      cerebral cortex or striatum of AF64A-treated animals. Administration of 
      nefiracetam (3 mg/kg, p.o.) twice daily for 9 days to AF64A-treated animals 
      ameliorated the deficit in active avoidance response in addition to attenuating 
      the increase in locomotor activities. In parallel with these behavioural effects, 
      nefiracetam reversed AF64A-induced alterations in the hippocampal profiles of 
      cholinergic and monoaminergic neurotransmitters and their metabolites. In 
      contrast, administration of phosphatidylcholine (30 mg/kg, p.o.) twice daily for 
      9 days had no significant effect on the deficit in active avoidance response, 
      despite significantly reversing the decrease in acetylcholine levels in the 
      hippocampus. These results indicate that the effects of nefiracetam on 
      AF64A-induced behavioural deficits are probably due to its ability to facilitate 
      both cholinergic and monoaminergic neurotransmitter systems.
FAU - Abe, E
AU  - Abe E
AD  - Department of Pharmacology, School of Dentistry, Iwate Medical University, 
      Morioka, Japan.
FAU - Murai, S
AU  - Murai S
FAU - Saito, H
AU  - Saito H
FAU - Masuda, Y
AU  - Masuda Y
FAU - Takasu, Y
AU  - Takasu Y
FAU - Shiotani, T
AU  - Shiotani T
FAU - Tachizawa, H
AU  - Tachizawa H
FAU - Itoh, T
AU  - Itoh T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - Austria
TA  - J Neural Transm Gen Sect
JT  - Journal of neural transmission. General section
JID - 9002201
RN  - 0 (Aziridines)
RN  - 0 (Biogenic Monoamines)
RN  - 0 (Neuromuscular Blocking Agents)
RN  - 0 (Phosphatidylcholines)
RN  - 0 (Pyrrolidinones)
RN  - 1JK12GX30N (nefiracetam)
RN  - A668M9E227 (ethylcholine aziridinium)
RN  - N91BDP6H0X (Choline)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - Acetylcholine/*physiology
MH  - Animals
MH  - Avoidance Learning/*drug effects
MH  - Aziridines/antagonists & inhibitors/*toxicity
MH  - Biogenic Monoamines/*physiology
MH  - Brain Chemistry/*drug effects
MH  - Choline/*analogs & derivatives/antagonists & inhibitors/toxicity
MH  - Electroshock
MH  - Hippocampus/*drug effects/physiopathology
MH  - Injections, Intraventricular
MH  - Learning Disabilities/*chemically induced/physiopathology
MH  - Male
MH  - Mice
MH  - Motor Activity/drug effects
MH  - Neuromuscular Blocking Agents/*toxicity
MH  - Phosphatidylcholines/pharmacology
MH  - Pyrrolidinones/*pharmacology/therapeutic use
MH  - Random Allocation
MH  - Retention, Psychology/drug effects
MH  - Single-Blind Method
MH  - Synaptic Transmission/drug effects
EDAT- 1994/01/01 00:00
MHDA- 1994/01/01 00:01
CRDT- 1994/01/01 00:00
PHST- 1994/01/01 00:00 [pubmed]
PHST- 1994/01/01 00:01 [medline]
PHST- 1994/01/01 00:00 [entrez]
AID - 10.1007/BF01271565 [doi]
PST - ppublish
SO  - J Neural Transm Gen Sect. 1994;95(3):179-93. doi: 10.1007/BF01271565.