Noradrenergic terminals are the primary source of α2-adrenoceptor mediated dopamine release in the medial prefrontal cortex

Publication date: Available online 23 November 2018Source: Progress in Neuro-Psychopharmacology and Biological PsychiatryAuthor(s): Paola Devoto, Giovanna Flore, Pierluigi Saba, Simona Scheggi, Giovanna Mulas, Carla Gambarana, Saturnino Spiga, Gian Luigi GessaAbstractIn various psychiatric disorders, deficits in dopaminergic activity in the prefrontal cortex (PFC) are implicated. Treatments involving selective augmentation of dopaminergic activity in the PFC primarily depend on the inhibition of α2-adrenoreceptors singly or in combination with the inhibition of the norepinephrine transporter (NET).We aimed to clarify the relative contribution of dopamine (DA) release from noradrenergic and dopaminergic terminals to DA output induced by blockade of α2-adrenoreceptors and NET. To this end, we assessed whether central noradrenergic denervation modified catecholamine output in the medial PFC (mPFC) of rats elicited by atipamezole (an α2-adrenoreceptor antagonist), nisoxetine (an NET inhibitor), or their combination.Intraventricular administration of anti-dopamine-beta-hydroxylase-saporin (aDBH) caused a loss of DBH-positive fibers in the mPFC and almost total depletion of tissue and extracellular NE level; however, it did not reduce tissue DA level but increased extracellular DA level by 70% in the mPFC. Because noradrenergic denervation should have caused a loss of NET and reduced NE level at α2-adrenoceptors, the actual effect of an aDBH-induced lesion on DA output elicited...
Source: Progress in Neuro Psychopharmacology and Biological Psychiatry - Category: Psychiatry Source Type: research