title: Hippocampal α-adrenoceptors involve in the effect of histamine on spatial learning.
abstract: Spatial learning is a model of higher human cognitive functions which is used for studying animal behavior. Histaminergic and noradrenergic systems play a modulatory role in learning and memory. The present study aimed to test the effects of α-adrenoceptor agonist/antagonist microinjection into the CA1 region of dorsal hippocampus on histamine-induced spatial learning facilitation in the water maze task. Pre-training intra-CA1 microinjection of α1- or α2-adrenergic agonist, phenylephrine (0.0025μg/rat) or clonidine (0.05μg/rat) decreased traveled distance and escape latency at the start of the training phase, suggesting a spatial learning facilitation; while the higher dose of the drugs (phenylephrine 0.005μg/rat, clonidine 0.2 and 0.5μg/rat) increased the performance level at the end of the training phase, indicating a water maze spatial acquisition impairment. However, α1-receptor antagonist, prazosin (1μg/rat) impaired spatial learning; α2-receptor antagonist, yohimbine (0.25μg/rat) facilitated spatial acquisition. Moreover, pre-training intra-CA1 microinjection of a subthreshold dose of phenylephrine (0.001μg/rat) reversed histamine response, while ineffective dose co-administration of clonidine (0.1μg/rat) potentiated histamine (0.01μg/rat) response. Subthreshold dose of prazosin or yohimbine did not alter histamine response. Bilateral infusion of histamine (0.05μg/rat) facilitated spatial learning by itself. Furthermore, the drug's injections had no effect on swimming speed on the training days of MWM. These results suggest that α-adrenergic receptors of the dorsal hippocampal CA1 regions may play an important role in histamine-induced facilitation of spatial acquisition.
authors.affiliation: Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Anahita
authors.initials: A
authors.lastname: Torkaman-Boutorabi
authors.affiliation: Department of Biology, Sciences and Research Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Danyali
authors.affiliation: Department of Biology, Sciences and Research Branch, Islamic Azad University, Tehran, Iran.
authors.forename: Shahrbanoo
authors.initials: S
authors.lastname: Oryan
authors.affiliation: Department of Biology, Faculty of Basic Sciences, University of Zanjan, Zanjan, Iran.
authors.forename: Mohaddeseh
authors.initials: M
authors.lastname: Ebrahimi-Ghiri
authors.affiliation: Department of Neuroscience, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran; School of Cognitive Sciences, Institute for Research in Fundamental Sciences, Tehran, Iran; Institute for Cognitive Science Studies, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: zarinmr@ams.ac.ir.
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Zarrindast
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology*; D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D013647:Task Performance and Analysis; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D018663:Adrenergic Agents; D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D017442:Histamine Agonists; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D010656:Phenylephrine; D015016:Yohimbine; D006632:Histamine; D003000:Clonidine; D011224:Prazosin
keywords: Clonidine; Histamine; Morris water maze; Phenylephrine; Prazosin; Rats; Yohimbine