The antagonistic effects of tetrahydroprotoberberines on dopamine receptors: electrophysiological studies

Abstract

Tetrahydroprotoberberines (THPBs), including (-)-stepholidine ((-)-SPD), (-)-tetrahydropalmatine ((-)-THP) and tetrahydroberberine (THB), have been demonstrated to be a new class of DA antagonists in biochemical and neuropharmacological studies. In this paper, the antagonistic action of THPBs was examined by means of single unit recording from nigral DA neuron in chloral hydrate-anesthetized and gallamine-paralyzed rats. Intravenous injection of these compounds could promptly and completely reverse the inhibition of the spontaneous firing induced by DA agonist apomorphine (APO) in a dose-dependent way. Pretreatment with (-)-SPD, (-)-THP or THB could significantly reduce the inhibitory effect of APO and shift the dose-action curve to the right. Besides, the compounds could increase the spontaneous firing of DA neurons. The above results not only strongly support the conclusion that (-)-SPD, (-)-THP and THB are DA antagonists, but also demonstrate that one of their blocking sites is at somatodendritic DA autoreceptors (D-2 receptors). In other words, (-)-SPD did not exhibit any DA agonistic action in this acute electrophysiological study, although its DA agonistic action can be demonstrated in rotational behavior of 6-OHDA-lesioned rats. The dual actions of (-)-SPD, dependent upon different experimental conditions, are discussed.