Histamine axons originate solely from the tuberomamillary nucleus (TMN) to innervate almost all brain regions. This feature is consistent with a function for histamine over a host of physiological processes, including regulation of appetite, body temperature, cognitive processes, pain perception and sleepewake cycle. An important question is whether these diverse physiological roles are served by different histamine neuronal subpopulations. Here we report that systemic administration of the non-imidazole histamine H3 receptor antagonist 4-(2-{2-[(2R)-2-methylpyrrolidinyl]ethyl}-benzofuran-5-yl)benzonitrile (ABT-239, 3 mg/kg) increased c-Fos expression dose-dependently in rat cortex and nucleus basalis magnocellularis (NBM) but not in the nucleus accumbens (NAcc) nor striatum, and augmented acetylcholine and histamine release from rat prefrontal cortex. To further understand functional histaminergic pathways in the brain, dual-probe microdialysis was used to pharmacologically block H3 receptors in the TMN. Perfusion of the TMN with ABT-239 (10 mM) increased histamine release from the TMN, NBM, and cortex, but not from the striatum or NAcc. When administered locally, ABT-239 increased histamine release from the NBM, but not from the NAcc. Systemic as well as intra-TMN administration of ABT-239 increased c-Fos expression in the NBM, and cortex, but not in the striatum or NAcc. Thus, as defined by their sensitivity to ABT-239, histaminergic neurons establish distinct pathways according to their terminal projections, and can differentially modulate neurotransmitter release in a brain regionspecific manner. This implies independent functions of subsets of histamine neurons according to their terminal projections, with relevant consequences for the development of specific compounds that affect only subsets of histamine neurones, thus increasing target specificity.

Selective brain region activation by histamine H(3) receptor antagonist/inverse agonist ABT-239 enhances acetylcholine and histamine release and increases c-fos expression / Leonardo Munari, Gustavo Provensi, Maria Beatrice Passani, Patrizio Blandina. - In: NEUROPHARMACOLOGY. - ISSN 0028-3908. - STAMPA. - 70:(2013), pp. 131-140. [10.1016/j.neuropharm.2013.01.021]

Selective brain region activation by histamine H(3) receptor antagonist/inverse agonist ABT-239 enhances acetylcholine and histamine release and increases c-fos expression.

Leonardo Munari;Gustavo Provensi;Maria Beatrice Passani;Patrizio Blandina
2013

Abstract

Histamine axons originate solely from the tuberomamillary nucleus (TMN) to innervate almost all brain regions. This feature is consistent with a function for histamine over a host of physiological processes, including regulation of appetite, body temperature, cognitive processes, pain perception and sleepewake cycle. An important question is whether these diverse physiological roles are served by different histamine neuronal subpopulations. Here we report that systemic administration of the non-imidazole histamine H3 receptor antagonist 4-(2-{2-[(2R)-2-methylpyrrolidinyl]ethyl}-benzofuran-5-yl)benzonitrile (ABT-239, 3 mg/kg) increased c-Fos expression dose-dependently in rat cortex and nucleus basalis magnocellularis (NBM) but not in the nucleus accumbens (NAcc) nor striatum, and augmented acetylcholine and histamine release from rat prefrontal cortex. To further understand functional histaminergic pathways in the brain, dual-probe microdialysis was used to pharmacologically block H3 receptors in the TMN. Perfusion of the TMN with ABT-239 (10 mM) increased histamine release from the TMN, NBM, and cortex, but not from the striatum or NAcc. When administered locally, ABT-239 increased histamine release from the NBM, but not from the NAcc. Systemic as well as intra-TMN administration of ABT-239 increased c-Fos expression in the NBM, and cortex, but not in the striatum or NAcc. Thus, as defined by their sensitivity to ABT-239, histaminergic neurons establish distinct pathways according to their terminal projections, and can differentially modulate neurotransmitter release in a brain regionspecific manner. This implies independent functions of subsets of histamine neurons according to their terminal projections, with relevant consequences for the development of specific compounds that affect only subsets of histamine neurones, thus increasing target specificity.
2013
70
131
140
Goal 3: Good health and well-being for people
Leonardo Munari, Gustavo Provensi, Maria Beatrice Passani, Patrizio Blandina
File in questo prodotto:
File Dimensione Formato  
13 Munari Neuropharmacology.pdf

Accesso chiuso

Tipologia: Pdf editoriale (Version of record)
Licenza: Tutti i diritti riservati
Dimensione 1.16 MB
Formato Adobe PDF
1.16 MB Adobe PDF   Richiedi una copia

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/791740
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 38
  • ???jsp.display-item.citation.isi??? 37
social impact