Effect of clobenpropit on regional cerebral blood flow in rat hippocampus

Area of Science:

• Neuroscience
• Pharmacology
• Physiology

Background:

• Histamine plays a role in regulating cerebral blood flow.
• Histamine receptors (H1, H2, H3) are present in the brain.
• The specific role of histamine in hippocampal blood flow is not fully understood.

Purpose of the Study:

• To investigate the effect of clobenpropit, an H3-antagonist, on regional cerebral blood flow (rCBF) in the rat hippocampus.
• To explore the involvement of histamine receptors in modulating hippocampal rCBF.

Main Methods:

• Regional cerebral blood flow (rCBF) was measured using the hydrogen clearance method in rats.
• Blood pressure was monitored non-invasively using a tail-cuff plethysmograph.
• Clobenpropit was administered intracerebroventricularly, with concurrent administration of other histamine receptor modulators.

Main Results:

• Intracerebroventricular injection of clobenpropit dose-dependently increased hippocampal rCBF.
• The effect of clobenpropit was potentiated by metoprine (histamine N-methyltransferase inhibitor).
• The clobenpropit-induced increase in rCBF was antagonized by H3-agonist, H1-antagonist (mepyramine), and H2-antagonist (zolantidine).
• Clobenpropit did not affect blood pressure.

Conclusions:

• Brain endogenous histamine contributes to increased rCBF in the rat hippocampus.
• Both post-synaptic H1 and H2 receptors, as well as pre-synaptic H3 receptors, are involved in histamine-mediated regulation of hippocampal blood flow.