Molecular mechanisms mediating gastrin-releasing peptide receptor modulation of memory consolidation in the hippocampus.
Although the gastrin-releasing peptide-preferring bombesin receptor (GRPR) has been implicated in memory formation, the underlying molecular events are poorly understood. In the present study, we examined interactions between the GRPR and cellular signaling pathways in influencing memory consolidation in the hippocampus. Male Wistar rats received bilateral infusions of bombesin (BB) into the dorsal hippocampus immediately after inhibitory avoidance (IA) training. Intermediate doses of BB enhanced, whereas a higher dose impaired, 24-h IA memory retention. The BB-induced memory enhancement was prevented by pretraining infusions of a GRPR antagonist or inhibitors of protein kinase C (PKC), mitogen-activated protein kinase (MAPK) kinase and protein kinase A (PKA), but not by a neuromedin B receptor (NMBR) antagonist. We next further investigated the interactions between the GRPR and the PKA pathway. BB-induced enhancement of consolidation was potentiated by coinfusion of activators of the dopamine D1/D5 receptor (D1R)/cAMP/PKA pathway and prevented by a PKA inhibitor. We conclude that memory modulation by hippocampal GRPRs is mediated by the PKC, MAPK, and PKA pathways. Furthermore, pretraining infusion of BB prevented beta-amyloid peptide (25-35)-induced memory impairment, supporting the view that the GRPR is a target for the development of cognitive enhancers for dementia.
Roesler
R
R
Cellular and Molecular Neuropharmacology Research Group, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, Campus Centro/UFRGS, Porto Alegre, RS, Brazil. rroesler@terra.com.br
Luft
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T
Oliveira
S H S
SH
Farias
C B
CB
Almeida
V R
VR
Quevedo
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J
Dal Pizzol
F
F
Schröder
N
N
Izquierdo
I
I
Schwartsmann
G
G
D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008568:Memory; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018004:Receptors, Bombesin / Q000819:agonists / Q000502:physiology*; D050641:Receptors, Dopamine D5 / Q000819:agonists; D015398:Signal Transduction
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D018004:Receptors, Bombesin; C074636:amyloid beta-protein (25-35); D050641:Receptors, Dopamine D5; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D020929:Mitogen-Activated Protein Kinase Kinases; D001839:Bombesin