title: Phosphoinositide 3-kinase is required for bombesin-induced enhancement of fear memory consolidation in the hippocampus.
abstract: Increasing evidence indicates that the neuronal gastrin-releasing peptide-preferring bombesin receptor (GRPR) is a key molecular regulator of fear memory formation. However, the downstream signaling events remain poorly understood. The protooncogene product phosphoinositide 3-kinase (PI3K) has been implicated in regulating memory formation, as well as in mediating cellular responses to GRPR activation in glioma and neuroblastoma cells. We show here that GRPR modulation of fear memory consolidation in the rat hippocampus requires PI3K activation. Male Wistar rats received bilateral infusions of the GRPR agonist bombesin (BB) or the PI3K inhibitor LY294002 into the CA1 region of the dorsal hippocampus immediately after inhibitory avoidance (IA) conditioning. BB enhanced, whereas LY294002 impaired, IA memory retention. The BB-induced memory enhancement was blocked by coinfusion of either a GRPR antagonist or LY294002. These findings provide the first evidence suggesting that PI3K signaling is required for GRPR regulation of CNS function.
authors.affiliation: Department of Pharmacology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil. rroesler@terra.com.br
authors.forename: Rafael
authors.initials: R
authors.lastname: Roesler
authors.forename: Samira S
authors.initials: SS
authors.lastname: Valvassori
authors.forename: Adalberto A
authors.initials: AA
authors.lastname: Castro
authors.forename: Tatiana
authors.initials: T
authors.lastname: Luft
authors.forename: Gilberto
authors.initials: G
authors.lastname: Schwartsmann
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
mesh_terms: D000818:Animals; D001839:Bombesin / Q000494:pharmacology*; D005239:Fear / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology* / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018004:Receptors, Bombesin / Q000378:metabolism
chemical_list: D018004:Receptors, Bombesin; D019869:Phosphatidylinositol 3-Kinases; D001839:Bombesin