title: Ventral hippocampal histamine increases the frequency of evoked theta rhythm but produces anxiolytic-like effects in the elevated plus maze.
abstract: The neurobiological underpinnings of anxiety are of paramount importance to the development of effective therapeutic treatments. To date, there is considerable pharmacological evidence suggesting that the suppression of hippocampal theta frequency is a robust and predictive assay of anxiolytic drug action. Recently, this idea has been challenged using histamine (2-(4-imidazolyl)ethanamine), an endogenous neurotransmitter involved in a number of brain and behavioral functions. Here, we systematically evaluate the effects of dorsal and ventral hippocampal histamine infusions on evoked theta frequency and behavioral anxiety. Given the complex pharmacological profile of histamine and its receptors in the hippocampus, we reasoned that local intra-hippocampal infusions would be a powerful test of the theta suppression model. While dorsal hippocampal infusions of histamine produced neither significant changes in anxious-like behavior in the elevated plus maze nor changes of evoked theta, ventral infusions of histamine produced potent behavioral anxiolysis which corresponded to an increase, and not a decrease, in evoked theta frequency. As a positive neurophysiological control, we demonstrated that diazepam, a proven anxiolytic drug, decreased the frequency of hippocampal theta following both dorsal and ventral hippocampal infusions. Our results further challenge the hippocampal theta frequency suppression model as a measure of anxiolytic drug action. This article is part of the Special Issue entitled 'Histamine Receptors'.
authors.affiliation: Department of Psychology, University of Alberta, P-217 Biological Sciences Building, Edmonton, AB T6G 2E9, Canada.
authors.forename: Michelle
authors.initials: M
authors.lastname: Yeung
authors.affiliation: Department of Psychology, University of Alberta, P-217 Biological Sciences Building, Edmonton, AB T6G 2E9, Canada; Neuroscience, 4-4142 Katz Group Centre, University of Alberta, Edmonton, AB T6G 2E1, Canada. Electronic address: dtreit@ualberta.ca.
authors.forename: Dallas
authors.initials: D
authors.lastname: Treit
authors.affiliation: Department of Psychology, University of Alberta, P-217 Biological Sciences Building, Edmonton, AB T6G 2E9, Canada; Neuroscience, 4-4142 Katz Group Centre, University of Alberta, Edmonton, AB T6G 2E1, Canada; Department of Physiology, 7-55 Medical Sciences Building, University of Alberta, Edmonton, AB T6G 2H7, Canada.
authors.forename: Clayton T
authors.initials: CT
authors.lastname: Dickson
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy* / Q000378:metabolism; D002408:Catheters, Indwelling; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006632:Histamine / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D023421:Models, Animal; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D013826:Theta Rhythm / Q000187:drug effects* / Q000502:physiology
chemical_list: D014151:Anti-Anxiety Agents; D006632:Histamine; D003975:Diazepam
keywords: Anxiety; Elevated plus-maze; Hippocampus; Histamine; Oscillation; Theta suppression model