Functional heterogeneity of the responses of histaminergic neuron subpopulations to various stress challenges

I. H. Miklós, K. J. Kovács

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66 Citations (Scopus)


In rats, the cell bodies of the histaminergic neuronal system are clustered in five distinct cell groups (E1-E5) within the posterior hypothalamus. On the basis of tract tracing studies, these histaminergic subgroups have been regarded as one functional unit. In addition to its well-characterized role in arousal, locomotor activity, metabolism, feeding, drinking and behaviour, as well as in coordination of autonomic functions, histamine has been implicated in regulation of the hypothalamo-pituitary- adrenocortical axis during stress. To address the capacity of different histaminergic subgroups to respond to various challenges, we revealed c-Fos, the immediate early gene marker of activated neurons, in histamine synthesizing neurons by combining c-Fos immunocytochemistry with in situ hybridization of histidine decarboxylase (HDC) mRNA. Compared to the negligible colocalization of these markers in control rats, restraint, insulin-induced hypoglycaemia and foot shock resulted in specific activation of histamine synthesizing neurons of the E4 and E5 subgroup in the tuberomammillary region. Up to 36% of HDC mRNA-expressing cells show c-Fos immunoreactivity in the E5 region. In addition, some neurons of the E1, E2 and E3 histaminergic groups were activated after restraint stress. Many less c-Fos-positive histaminergic neurons were detected after immobilization and dehydration. Ether stress, acute hyperosmotic stimulus or injection of bacterial lipopolysaccharide did not activate hypothalamic HDC-positive neurons. These results suggest, for the first time, the functional heterogeneity of histaminergic neuron population, the components of which are recruited in a stressor- and subgroup-specific manner.

Original languageEnglish
Pages (from-to)3069-3079
Number of pages11
JournalEuropean Journal of Neuroscience
Issue number11
Publication statusPublished - Dec 1 2003


  • Histamine
  • Histidine decarboxylase
  • Rat
  • Tuberomammillary nucleus
  • c-Fos

ASJC Scopus subject areas

  • Neuroscience(all)

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