Anxiety and cognition in histamine H3 receptor-/- mice.
Histamine H(3) receptors (H3Rs) were first characterized as autoreceptors modulating histamine release and synthesis via negative feedback. Acute H3R stimulation or blockade with selective agonists and antagonists suggests a role for H3R in anxiety and cognition. However, little is known about the long-term effects of H3R blockade on brain function. In the current study, mice lacking H3 receptors (H3R(-/-)) were used to investigate the role of H3R-mediated signalling in anxiety and cognition. H3R(-/-) mice showed enhanced spatial learning and memory in the Barnes maze. In addition, H3R(-/-) mice showed reduced measures of anxiety in the elevated plus and zero mazes involving exploratory behaviour and avoidable anxiety-provoking stimuli, but enhanced acoustic startle responses involving unavoidable anxiety-provoking stimuli. These behavioural alterations were associated with higher arginine vasopressin levels in the central and basolateral nuclei of the amygdala. These findings support a role for H3Rs in mediating histamine effects on spatial learning and memory and measures of anxiety.
Rizk
Angela
A
Department of Behavioural Neuroscience, Oregon Health and Science University, 3181 SW. Sam Jackson Park Road, Portland, OR 97239, USA.
Curley
Justine
J
Robertson
Jennifer
J
Raber
Jacob
J
D000679:Amygdala / Q000033:anatomy & histology / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000503:physiopathology*; D001127:Arginine Vasopressin / Q000378:metabolism; D001522:Behavior, Animal; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000235:genetics / Q000503:physiopathology*; D004307:Dose-Response Relationship, Radiation; D005106:Exploratory Behavior / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology; D011930:Reaction Time; D018100:Receptors, Histamine H3 / Q000502:physiology*; D012022:Reflex, Acoustic / Q000502:physiology / Q000528:radiation effects; D013037:Spatial Behavior / Q000502:physiology; D018709:Statistics, Nonparametric; D013997:Time Factors
D018100:Receptors, Histamine H3; D001127:Arginine Vasopressin