title: 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.
abstract: Adult male Wistar rats were bilaterally implanted with indwelling cannulae in the CA1 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-microl infusion of saline, or of LY294002 (5, 50 or 500 microM), 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.
authors.affiliation: Departamento de Ciências Fisiológicas, Setor de Farmacologia, Fundação Universidade Federal de Rio Grande, Rio Grande, Brazil. izquier@terra.com.br
authors.forename: D M
authors.initials: DM
authors.lastname: Barros
authors.forename: T
authors.initials: T
authors.lastname: Mello e Souza
authors.forename: M M
authors.initials: MM
authors.lastname: de Souza
authors.forename: H
authors.initials: H
authors.lastname: Choi
authors.forename: T
authors.initials: T
authors.lastname: DeDavid e Silva
authors.forename: G
authors.initials: G
authors.lastname: Lenz
authors.forename: J H
authors.initials: JH
authors.lastname: Medina
authors.forename: I
authors.initials: I
authors.lastname: Izquierdo
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D002867:Chromones / Q000008:administration & dosage / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D008845:Microinjections; D009025:Morpholines / Q000008:administration & dosage / Q000494:pharmacology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one