LY294002, an inhibitor of phosphoinositide 3-kinase given into rat hippocampus impairs acquisition, consolidation and retrieval of memory for one-trial step-down inhibitory avoidance

被引:66
作者
Barros, DM
Souza, TME
de Souza, MM
Choi, H
Silva, TDE
Lenz, G
Medina, JH
Izquierdo, I
机构
[1] Univ Fed Rio Grande do Sul, Inst Ciencias Basicas Saude, Dept Bioquim, Ctr Memoria, BR-90035003 Porto Alegre, RS, Brazil
[2] Fundacao Univ Fed Rio Grande, Setor Farmacol, Dept Ciencias Fisiol, Rio Grande, Brazil
[3] Univ Fed Rio Grande do Sul, Inst Biociencias, Dept Biofis, BR-90049 Porto Alegre, RS, Brazil
[4] Univ Buenos Aires, Fac Med, Inst Biol Celular & Neurociencia Eduardo de Rober, Buenos Aires, DF, Argentina
来源
BEHAVIOURAL PHARMACOLOGY | 2001年 / 12卷 / 08期
关键词
LY294002; PI3-K; inhibitory avoidance; retrieval; memory; rat;
D O I
10.1097/00008877-200112000-00007
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
Adult male Wistar rats were bilaterally implanted with indwelling cannulae in the CAI region of the dorsal hippocampus. Once recovered from surgery, animals were submitted to one session of step-down inhibitory avoidance training (3.0 s, 0.4 mA footshock). Animals received a 0.5-mul infusion of saline, or of LY294002 (5, 50 or 500 muM), an inhibitor of the phosphoinositide 3-kinase (PI 3-K) family. Infusions were given 10 min before training, immediately post-training or 10 min prior to a 24-h retention test. In the pre- and post-training groups, the animals were tested twice: at 1.5 and 24 h after training, for short- (STM) and long-term memory (LTM), respectively. Pre- and post-training infusion of the drug inhibited both STM and LTM. Pre-test infusions impaired LTM retrieval. The effects can not be attributed to influences on locomotor, exploratory, pro- or anti-conflict behaviour, since LY294002 had no influence on elevated plus-maze behaviour. The results suggest that hippocampal PI 3-K is necessary for memory acquisition, consolidation and retrieval of the consolidation of step-down inhibitory avoidance in rats. This could be due to an interaction with the N-methyl-D-aspartate (NMDA) receptor complex or with activity of the extracellularly regulated protein kinase (ERK)-Ras signalling pathway. (C) 2001 Lippincott Williams & Wilkins.
引用
收藏
页码:629 / 634
页数:6
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