Release of acetylcholine in the ventral striatum is influenced by histamine receptors

To investigate whether histamine receptor ligands influence the in vivo-release of acetylcholine in the ventral striatum, this brain region was superfused with histamine receptor agonists or antagonists through a push-pull cannula and drug effects on the release of acetylcholine were investigated. Histamine, the H1 receptor agonist 2-thiazolyl-ethylamine and the H3 receptor antagonist thioperamide enhanced acetylcholine release, while the H3 receptor agonist (R)-alpha-methylhistamine was ineffective. The results indicate that H1 receptors and H3 receptors modulate acetylcholine release. The thioperamide-induced increase of acetylcholine release might be exerted via H3-receptors located on cholinergic terminals. Alternatively, thioperamide might enhance acetylcholine release by increasing endogenous histamine release via H3 autoreceptors. It is concluded that, via stimulation of striatal H1- and H3 receptors, histaminergic neurons are involved in the regulation of cholinergic neuronal activity in the ventral striatum.