G.F. and E.D. contributed equally to this work.
The role of cortical and hypothalamic histamine-3 receptors in the modulation of central histamine neurotransmission: an in vivo electrophysiology and microdialysis study
Article first published online: 2 NOV 2011
© 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience
Volume 34, Issue 11, pages 1747–1755, December 2011
How to Cite
Flik, G., Dremencov, E., Cremers, T. I. H. F., Folgering, J. H. A. and Westerink, B. H. C. (2011), The role of cortical and hypothalamic histamine-3 receptors in the modulation of central histamine neurotransmission: an in vivo electrophysiology and microdialysis study. European Journal of Neuroscience, 34: 1747–1755. doi: 10.1111/j.1460-9568.2011.07893.x
- Issue published online: 28 NOV 2011
- Article first published online: 2 NOV 2011
- Received 6 July 2011, revised 2 September 2011, accepted 2 September 2011
- prefrontal cortex (PFC);
- tuberomammillary nucleus (TMN)
The current study aimed to investigate the effect of histamine-3 (H3) receptors, expressed in the tuberomammillary nucleus (TMN) of the hypothalamus and in the prefrontal cortex (PFC), on histamine neurotransmission in the rat brain. The firing activity of histamine neurons in the TMN was measured using in vivo extracellular single-unit electrophysiology, under propofol anesthesia. Extracellular histamine levels were determined using the dual (PFC and TMN) probe microdialysis, in freely-moving animals. Histamine levels in dialysates were determined using high-performance liquid chromatography (HPLC) and fluorescence detection. It was found that systemic administration of the selective H3-agonist, immepip, decreases, and the reverse H3/H4-agonist, thioperamide, increases the firing activity of histamine neurons in the TMN and the release of histamine in TMN and PFC. Local perfusion of immepip into the TMN increased, and thioperamide decreased, histamine levels in the TMN but not in the PFC. Local perfusion of immepip into the PFC, however, decreased extracellular histamine levels in both TMN and PFC. It can be concluded that brain H3 receptors, and especially those expressed in the PFC, play an important role in the autoregulation of histamine neurotransmission. It is possible that H3 receptors in the PFC are expressed on pyramidal neurons projecting to the TMN, and activation of these receptors diminishes glutamate excitatory input from PFC to the TMN. As the brain histamine system has a role in pathophysiology of psychotic, affective, cognitive, sleep and eating disorders, H3 receptors are potential targets for future CNS medications.