H3 Autoreceptors and muscarinic acetylcholine receptors modulate histamine release in the anterior hypothalamus of freely moving rats

To investigate the modulation of histamine release by autoreceptors and heteroreceptors, the rat anterior hypothalamus was superfused through a push-pull cannula with agonists or antagonists of histamine and acetylcholine muscarinic receptors. Superfusion with the H₃ receptor agonist (R)-α-methylhistamine inhibited, while superfusion with thioperamide (H₃ antagonist) enhanced histamine release. Superfusion with carbachol (a mixed M₁, M₂, M₃ agonist) inhibited the release of histamine. The release of endogenous histamine was enhanced on superfusion with atropine (a mixed M₁, M₂, M₃ antagonist). The M₃ muscarinic antagonist 4-diphenylacetoxy-N-methylpiperidine enhanced the release rate of histamine. It is concluded that in the anterior hypothalamus the release of endogenous histamine is modulated by H₃ autoreceptors. Moreover, acetylcholine released from cholinergic neurons also modulates the release of histamine via M₁ and/or M₃ heteroreceptors.