Research ReportThe modulatory action of harmane on serotonergic neurotransmission in rat brain

•Harmane selectively stimulates 5-HT release in rat brain cortex in vitro.•Harmane-induced 5-HT release was partly reduced in the absence of K+ and Ca2+ ions.•Other related β-carbolines also induced basal 5-HT release in rat brain cortex.

The naturally occurring β-carboline, harmane, has been implicated in various physiological and psychological conditions. Some of these effects are attributed to its interaction with monoaminergic systems. Previous literature indicates that certain β-carbolines including harmane modulate central monoamine levels partly through monoamine oxidase (MAO) inhibition. However, this is not always the case and thus additional mechanisms may be involved. This study set to assess the potential modulatory role of harmane on the basal or K+ stimulated release of preloaded radiolabelled noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in rat brain cortex in vitro in the presence of the MAO inhibitor pargyline. Harmane displayed an overt elevation in K+ -evoked [3H]5-HT release; whilst little and no effect was reported with [3H]DA and [3H]NA respectively. The effect of harmane on [3H]5-HT efflux was partially compensated in K+-free medium. Further analyses demonstrated that removal of Ca2+ ions and addition of 1.2 mM EGTA did not alter the action of harmane on [3H]5-HT release from rat brain cortex. The precise mechanism of action however remains unclear but is unlikely to reflect an involvement of MAO inhibition. The current finding aids our understanding on the modulatory action of harmane on monoamine levels and could potentially be of therapeutic use in psychiatric conditions such as depression and anxiety.