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Evidence for an ascending inhibitory histaminergic pathway to the cerebral cortex
Abstract:
Previous observations from our laboratory indicate that metiamide is a specific histamine antagonist in rat cerebral cortex. In view of the recent finding that histamine levels and L-histidine decarboxylase (EC 4.1.1.22) activity in cerebral cortex decrease following disruption of the ipsilateral medial forebrain bundle (MFB), the present investigation was undertaken to examine whether iontophoretically applied metiamide antagonizes the inhibition of deep cerebral cortical neurones produced by stimulation of the MFB. In rats anaesthetized with a mixture of methoxyflurane, nitrous oxide and oxygen, stimulation of the ipsilateral MFB or the cortical surface with iontophoretically applied histamine depressed the firing of cortical neurones. Metiamide antagonized the histamine-induced depression and reduced the duration of inhibition produced by MFB stimulation. However, it did not alter the inhibition induced by the cortical surface stimulation. These results indicate that a histaminergic pathway ascending through the MFB may inhibit rat cerebral cortical neurones.
Insights
Metiamide, a histamine antagonist, was tested on rat neurons. It blocked histamine effects and reduced inhibition from medial forebrain bundle stimulation, suggesting a histaminergic pathway influences cortical neuron activity.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Metiamide is a known histamine antagonist in the rat cerebral cortex.
- Histamine levels and L-histidine decarboxylase activity decrease in the cerebral cortex after medial forebrain bundle (MFB) disruption.
Purpose of the Study:
- To investigate if metiamide antagonizes neuronal inhibition caused by MFB stimulation.
- To explore the role of a potential histaminergic pathway in regulating cortical neuronal activity.
Main Methods:
- Iontophoretic application of histamine and metiamide in anesthetized rats.
- Stimulation of the medial forebrain bundle (MFB) and cortical surface.
- Recording of deep cerebral cortical neuronal firing rates.
Main Results:
- Metiamide antagonized histamine-induced neuronal depression.
- Metiamide reduced the duration of inhibition following MFB stimulation.
- Metiamide did not affect inhibition caused by direct cortical surface stimulation.
Conclusions:
- A histaminergic pathway ascending via the MFB likely inhibits rat cerebral cortical neurons.
- This study provides evidence for a descending inhibitory histaminergic pathway in the brain.