title: Heterogeneity of histaminergic neurons in the tuberomammillary nucleus of the rat.
abstract: Histaminergic neurons of the hypothalamic tuberomammillary nuclei (TMN) send projections to the whole brain. Early anatomical studies described histaminergic neurons as a homogeneous cell group, but recent evidence indicates that histaminergic neurons are heterogeneous and organized into distinct circuits. We addressed this issue using the double-probe microdialysis in freely moving rats to investigate if two compounds acting directly onto histaminergic neurons to augment cell firing [thioperamide and bicuculline, histamine H(3)- and gamma-aminobutyric acid (GABA)(A)-receptor (R) antagonists, respectively] may discriminate groups of histaminergic neurons impinging on different brain regions. Intra-hypothalamic perfusion of either drug increased histamine release from the TMN and cortex, but not from the striatum. Thioperamide, but not bicuculline, increased histamine release from the nucleus basalis magnocellularis (NBM), bicuculline but not thioperamide increased histamine release from the nucleus accumbens (NAcc). Intra-hypothalamic perfusion with thioperamide increased the time spent in wakefulness. To explore the local effects of H(3)-R blockade in the histaminergic projection areas, each rat was implanted with a single probe to simultaneously administer thioperamide and monitor local changes in histamine release. Thioperamide increased histamine release from the NBM and cortex significantly, but not from the NAcc or striatum. The presence of H(3)-Rs on histaminergic neurons was assessed using double-immunofluorescence with anti-histidine decarboxylase antibodies to identify histaminergic cells and anti-H(3)-R antibodies. Confocal analysis revealed that all histaminergic somata were immunopositive for the H(3)-R. This is the first evidence that histaminergic neurons are organized into functionally distinct circuits that influence different brain regions, and display selective control mechanisms.
authors.affiliation: Dipartimento di Farmacologia Preclinica e Clinica, V.le G. Pieraccini 6, Universitá di Firenze, 50139 Firenze, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Giannoni
authors.forename: Maria-Beatrice
authors.initials: MB
authors.lastname: Passani
authors.forename: Daniele
authors.initials: D
authors.lastname: Nosi
authors.forename: Paul L
authors.initials: PL
authors.lastname: Chazot
authors.forename: Fiona C
authors.initials: FC
authors.lastname: Shenton
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Medhurst
authors.forename: Leonardo
authors.initials: L
authors.lastname: Munari
authors.forename: Patrizio
authors.initials: P
authors.lastname: Blandina
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D020532:Basal Nucleus of Meynert / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D004525:Efferent Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D018756:GABA Antagonists / Q000494:pharmacology; D006632:Histamine / Q000378:metabolism*; D054828:Histamine H3 Antagonists / Q000494:pharmacology; D007026:Hypothalamic Area, Lateral / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018100:Receptors, Histamine H3 / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology
chemical_list: D018756:GABA Antagonists; D054828:Histamine H3 Antagonists; D018100:Receptors, Histamine H3; D006632:Histamine