Improvement in fear memory by histamine-elicited ERK2 activation in hippocampal CA3 cells.
Consolidation of associative memories appears to require extracellular signal-related kinase2 (ERK2) activation, which is modulated by several factors, including neurotransmitter receptor stimulation. Here we show that in vitro stimulation of either H2 or H3 histaminergic receptors activates ERK2 in hippocampal CA3 pyramidal cells. In behaving animals, bilateral posttraining injections into the dorsal hippocampus of histamine H2 or H3 receptor agonists improve memory consolidation after contextual fear conditioning. Local administration of U0126, a selective inhibitor of ERK kinase, prevents memory improvements exerted by the agonists, without causing any behavioral effect per se. This is the first evidence of a positive correlation between ERK phosphorylation and memory improvement. Moreover, we demonstrate that the brain histaminergic system regulates hippocampal ERK cascade. Finally, our data indicate that early ERK2 hippocampal activation is not required for the expression of long-term fear memories.
Giovannini
Maria Grazia
MG
Dipartimento di Farmacologia Preclinica e Clinica, Universitá di Firenze, 50139 Firenze, Italy.
Efoudebe
Marcel
M
Passani
Maria Beatrice
MB
Baldi
Elisabetta
E
Bucherelli
Corrado
C
Giachi
Filippo
F
Corradetti
Renato
R
Blandina
Patrizio
P
D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005239:Fear / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006632:Histamine / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008568:Memory / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000378:metabolism; D018100:Receptors, Histamine H3 / Q000187:drug effects / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology
D002070:Butadienes; D004791:Enzyme Inhibitors; D017442:Histamine Agonists; D006635:Histamine H2 Antagonists; D009570:Nitriles; D011970:Receptors, Histamine H2; D018100:Receptors, Histamine H3; D026941:Sodium Channel Blockers; C113580:U 0126; D006632:Histamine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases