Basic fibroblast growth factor prevents the memory impairment induced by gastrin-releasing peptide receptor antagonism in area CA1 of the rat hippocampus.
Increasing evidence indicates that the gastrin-releasing peptide receptor (GRPR) is implicated in regulating synaptic plasticity and memory formation in the hippocampus and other brain areas. However, the molecular mechanisms underlying the memory-impairing effects of GRPR antagonism have remained unclear. Here we report that basic fibroblast growth factor (bFGF/FGF-2) rescues the memory impairment induced by GRPR antagonism in the rat dorsal hippocampus. The GRPR antagonist [D-Tpi(6), Leu(13) psi(CH(2)NH)-Leu(14)] bombesin (6-14) (RC-3095) at 1.0 microg impaired, whereas bFGF at 0.25 microg enhanced, 24 h retention of inhibitory avoidance (IA) when infused immediately after training into the CA1 hippocampal area in male rats. Coinfusion with an otherwise ineffective dose of bFGF blocked the memory-impairing effect of RC-3095. These findings suggest that the memory-impairing effects of GRPR antagonists might be partially mediated by an inhibition in the function and/or expression of neuronal bFGF or diminished activation of intracellular protein kinase pathways associated with bFGF signaling.
Preissler
Thales
T
Department of Pharmacology, Institute for Basic Health Sciences, Cellular and Molecular Neuropharmacology Research Group, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
Luft
Tatiana
T
Kapczinski
Flávio
F
Quevedo
João
J
Schwartsmann
Gilberto
G
Roesler
Rafael
R
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001839:Bombesin / Q000031:analogs & derivatives / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000502:physiology; D008569:Memory Disorders / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors* / Q000378:metabolism
D018696:Neuroprotective Agents; D010446:Peptide Fragments; D018004:Receptors, Bombesin; D016222:Fibroblast Growth Factor 2; C071363:bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-; D001839:Bombesin