Histamine enhances inhibitory avoidance memory consolidation through a H2 receptor-dependent mechanism.
Several evidences suggest that brain histamine is involved in memory consolidation but the actual contribution of the hippocampal histaminergic system to this process remains controversial. Here, we show that when infused into the CA1 region of the dorsal hippocampus immediately after training in an inhibitory avoidance task, but not later, histamine induced a dose-dependent promnesic effect without altering locomotor activity, exploratory behavior, anxiety state or retrieval of the avoidance response. The facilitatory effect of intra-CA1 histamine was mimicked by the histamine N-methyltransferase inhibitor SKF-91844 as well as by the H2 receptor agonist dimaprit and it was blocked completely by the H2 receptor antagonist ranitidine. Conversely, the promnesic action of histamine was unaffected by the H1 receptor antagonist pyrilamine, the H3 receptor antagonist, thioperamide, and the NMDAr polyamine-binding site antagonist ifenprodil. By themselves, ranitidine, pyrilamine, thioperamide, and ifenprodil did not affect IA memory consolidation. Our data indicate that, when given into CA1, histamine enhances memory consolidation through a mechanism that involves activation of H2 receptors; however, endogenous CA1 histamine does not seem to participate in the consolidation of IA memory at least at the post-training times analyzed.
da Silva
Weber C
WC
Centro de Memória, Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
Bonini
Juliana S
JS
Bevilaqua
Lia R M
LR
Izquierdo
Iván
I
Cammarota
Martín
M
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006632:Histamine / Q000008:administration & dosage / Q000502:physiology*; D017442:Histamine Agonists / Q000008:administration & dosage; D006635:Histamine H2 Antagonists / Q000008:administration & dosage; D008297:Male; D008845:Microinjections; D018697:Nootropic Agents / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000502:physiology*; D012153:Retention, Psychology / Q000187:drug effects / Q000502:physiology*
D017442:Histamine Agonists; D006635:Histamine H2 Antagonists; D018697:Nootropic Agents; D011970:Receptors, Histamine H2; D006632:Histamine