Opposite effects of low and high doses of the gastrin-releasing peptide receptor antagonist RC-3095 on memory consolidation in the hippocampus: possible involvement of the GABAergic system.
Although the gastrin-releasing peptide receptor (GRPR) has recently emerged as a system importantly involved in regulating memory formation, the role of hippocampal GRPRs in memory remains controversial. The present study examined the effects of GRPR antagonism on memory consolidation in area CA1 of the hippocampus. Male Wistar rats received bilateral infusions of the GRPR antagonist [D-Tpi6, Leu13 psi(CH2NH)-Leu14] bombesin (6-14) (RC-3095; 1, 3, or 10 microg/side) into the dorsal hippocampus immediately after inhibitory avoidance (IA) training. RC-3095 at 1 microg impaired, whereas the dose of 10 microg enhanced, 24-h IA retention. A second experiment showed that the RC-3095-induced enhancement of memory consolidation was prevented by pretraining infusion of an otherwise ineffective dose of the gamma-aminobutyric acid type A (GABA(A)) receptor agonist muscimol. The results indicate that high doses of GRPR antagonists can induce enhancement of memory consolidation in the hippocampus. In addition, the memory-enhancing effect of GRPR antagonists might be mediated by inhibition of GABAergic transmission.
Dantas
Andrea dos Santos
Ados S
Cellular and Molecular Neuropharmacology Research Group, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, 90046-900 Porto Alegre, RS, Brazil.
Luft
Tatiana
T
Henriques
João Antônio Pêgas
JA
Schwartsmann
Gilberto
G
Roesler
Rafael
R
D000818:Animals; D001839:Bombesin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018682:GABA Agents / Q000008:administration & dosage* / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008568:Memory / Q000187:drug effects*; D008954:Models, Biological; D009118:Muscimol / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*
D018682:GABA Agents; D058785:GABA-A Receptor Agonists; D010446:Peptide Fragments; D018004:Receptors, Bombesin; D011963:Receptors, GABA-A; C071363:bombesin (6-14), Tpi(6)-Leu(13)-psi(CH2NH)-Leu(14)-; C076540:bombesin (6-14), D-Trp(6)-Leu(13)-psi(CH2NH)-Leu(14)-; D009118:Muscimol; D001839:Bombesin