Yohimbine acts as a putative in vivo alpha2A/D-antagonist in the rat prefrontal cortex.

Yohimbine has been widely used as alpha2-adrenergic receptor antagonist in neurophysiological research and in clinical therapy. In this study, we provide in vivo electrophysiological evidence, that microiontophoretic application of yohimbine (YOH) inhibits spontaneous activity of prefrontal neurons of the rat. By microiontophoretic application of the alpha2A-receptor antagonist BRL44408 (BRL), the effects of YOH could be mimicked, indicating that the action of YOH is manifested through alpha2A/D-receptor mechanisms. Furthermore, the inhibiting effects of YOH or BRL were blocked by alpha2B-receptor antagonist imiloxan. In concert with previous microiontophoretic data, the present findings suggest that alpha2-receptor antagonist YOH predominantly acts on the alpha2A/D-receptor subtype in vivo. Furthermore, we hypothesize that this action is manifested via deactivation of autoreceptors causing increased norepinephrine release, finally inhibiting postsynaptic neurons through the activation of alpha2B-receptors.