title: Alpha 2-adrenergic receptor-mediated presynaptic inhibition of GABAergic IPSPs in rat histaminergic neurons.
abstract: Nuclei of the brainstem involved in behavioral state control are mutually interconnected. Histaminergic neurons of the posterior hypothalamus receive inputs from brainstem noradrenergic cell groups as well as from the locus coeruleus. The role of adrenergic inputs in histaminergic function is unclear. We examined the actions of adrenergic agonists on histaminergic neurons of the tuberomamillary nucleus (TM) using electrophysiological methods in a brain slice preparation. Evoked GABAergic inhibitory postsynaptic potentials (IPSPs) in histaminergic neurons were reduced in amplitude following the application of norepinephrine (NE) (2-20 microM) or clonidine (10 microM) but were not affected by isoproterenol (10 microM). Norepinephrine application caused no changes in membrane properties of TM neurons. Responses to exogenously applied GABA were unaffected by adrenergic agonists. Clonidine reduced the frequency of spontaneous IPSPs, an action that was blocked by yohimbine. Norepinephrine did not alter the amplitude distribution of bicuculline-sensitive miniature inhibitory postsynaptic currents (mIPSCs). Thus, GABA release onto TM neurons is modulated presynaptically by adrenergic alpha(2)-receptors. Inputs from noradrenergic neurons of the brainstem will reduce the inhibitory actions of GABAergic inputs resulting in disinhibition of histaminergic neurons.
authors.affiliation: Department of Neurophysiology, Heinrich-Heine Universität, Postfach 101007, D-40001 Duesseldorf, Germany. phdste@uniklinik-saarland.de
authors.forename: David R
authors.initials: DR
authors.lastname: Stevens
authors.forename: Atsuo
authors.initials: A
authors.lastname: Kuramasu
authors.forename: Krister S
authors.initials: KS
authors.lastname: Eriksson
authors.forename: Oliver
authors.initials: O
authors.lastname: Selbach
authors.forename: Helmut L
authors.initials: HL
authors.lastname: Haas
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D005260:Female; D006632:Histamine / Q000502:physiology*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000502:physiology*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D018341:Receptors, Adrenergic, alpha-2; D015016:Yohimbine; D005680:gamma-Aminobutyric Acid; D006632:Histamine; D009638:Norepinephrine