Journal of Molecular Neuroscience

, Volume 56, Issue 2, pp 320–328 | Cite as

Interaction Between Brain Histamine and Serotonin, Norepinephrine, and Dopamine Systems: In Vivo Microdialysis and Electrophysiology Study

  • Gunnar Flik
  • Joost H. A. Folgering
  • Thomas I. H. F. Cremers
  • Ben H. C. Westerink
  • Eliyahu Dremencov


Brain monoamines (serotonin, norepinephrine, dopamine, and histamine) play an important role in emotions, cognition, and pathophysiology and treatment of mental disorders. The interactions between serotonin, norepinephrine, and dopamine were studied in numerous works; however, histamine system received less attention. The aim of this study was to investigate the interactions between histamine and other monoamines, using in vivo microdialysis and electrophysiology. It was found that the inverse agonist of histamine-3 receptors, thioperamide, increased the firing activity of dopamine neurons in the ventral tegmental area. Selective agonist of histamine-3 receptors, immepip, reversed thiperamide-induced stimulation of firing activity of dopamine neurons. The firing rates of serotonin and norpeinephrine neurons were not attenuated by immepip or thioperamide. Thioperamide robustly and significantly increased extracellular concentrations of serotonin, norepinephrine, and dopamine in the rat prefrontal cortex and slightly increased norepinephrine and dopamine levels in the tuberomammillary nucleus of the hypothalamus. It can be concluded that histamine stimulates serotonin, norepinephrine, and dopamine transmission in the brain. Modulation of firing of dopamine neurons is a key element in functional interactions between histamine and other monoamines. Antagonists of histamine-3 receptors, because of their potential ability to stimulate monoamine neurotransmission, might be beneficial in the treatment of mental disorders.


Histamine-3 (H3) receptors Thioperamide Immepip Tuberomammillary nucleus (TMN) of hypothalamus Dorsal raphe nucleus (DRN) Locus coeruleus (LC) Ventral tegmental area (VTA) Prefrontal cortex (PFC) 



The authors thank Ms K Jansen, Mr H Kooijker, and Ms S Postma for technical assistance and Dr L Lacinova for critical proof-reading of this manuscript.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Brains On-Line BVGroningenThe Netherlands
  2. 2.Institute of Molecular Physiology and GeneticsSlovak Academy of ScienceBratislavaSlovakia
  3. 3.Institute of Experimental EndocrinologySlovak Academy of ScienceBratislavaSlovakia

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