title: Involvement of the dorsal hippocampal dopamine D2 receptors in histamine-induced anxiogenic-like effects in mice.
abstract: Anxiety-related behaviors increase histamine and dopamine release in the brain. On the other hand, central histamine counteracts reward and reinforcement processes mediated by the mesolimbic dopamine system. We investigated the effects of the histaminergic system and dopamine D2 receptors agents and their interactions on anxiety-related behaviors using the elevated plus-maze (EPM). The intra-hippocampal (Intra-CA1) microinjection of histamine (10 μg/mouse) decreased the percentage of open arm time (%OAT) and open arm entries (%OAE) but not the locomotor activity, indicating an anxiogenic-like response. Quinpirole (0.5 and 2 μg/mouse) or sulpiride (0.3 and 1 μg/mouse) when injected into the dorsal hippocampus also induced anxiety-like behavior, however, the drugs reversed the anxiogenic response induced by the effective dose of histamine (10 μg/mouse). Taken together and under the present experimental design, our results indicate that activation of the dorsal hippocampal histaminergic receptors causes anxiety-like behaviors altered by dopamine D2 receptor agonist and antagonist. Histamine can decrease dopaminergic tone in the dorsal hippocampus through decreasing the endogenous dopamine release, whereas quinpirole does the same via the postsynaptic DA receptors' activation. Sulpiride however renders the same effect through autoreceptors' blockade and potentiated dopamine transmission. Thus, quinpirole and sulpiride seem to compensate the effects of the intra-CA1 injection of exogenous histamine, and tend to exert anxiolytic effects in the presence of histamine.
authors.affiliation: Department of Biology, Faculty of Basic Sciences, Islamic Azad University, Ardabil Branch, Ardabil, Iran.
authors.forename: Morteza
authors.initials: M
authors.lastname: Piri
authors.forename: Elham
authors.initials: E
authors.lastname: Ayazi
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Zarrindast
mesh_terms: D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D019257:Quinpirole / Q000494:pharmacology; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013469:Sulpiride / Q000494:pharmacology
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D013469:Sulpiride; D006632:Histamine
keywords: Anxiety-like behavior; Dopamine D2 receptors; Elevated plus maze; Histamine; Mice