Journal Article

Inhibition of Morphine- and Ethanol-Mediated Stimulation of Mesolimbic Dopamine Neurons by Withania somnifera

Kasture, Sanjay B., Talani, Giuseppe, Porru, Simona, Bassareo, Valentina, Frau, Roberto, Loi, Eleonora, Sanna, Enrico, Rosas, Michela, Peana, Alessandra T., Acquas, Elio

2019

Overview

Morphine- and ethanol-induced stimulation of neuronal firing of ventral tegmental area (VTA) dopaminergic neurons and of dopamine (DA) transmission in the shell of the nucleus accumbens (AcbSh) represents a crucial electrophysiological and neurochemical response underlying the ability of these compounds to elicit motivated behaviors and trigger a cascade of plasticity-related biochemical events. Previous studies indicate that the standardized methanolic extract of roots (WSE) prevents morphine- and ethanol-elicited conditioned place preference and oral ethanol self-administration. Aim of the present research was to investigate whether WSE may also interfere with the ability of morphine and ethanol to stimulate VTA dopaminergic neurons and thus AcbSh DA transmission as assessed in male Sprague-Dawley rats by means of patch-clamp recordings in mesencephalic slices and brain microdialysis, respectively. Morphine and ethanol significantly stimulated spontaneous firing rate of VTA neurons and DA transmission in the AcbSh. WSE, at concentrations (200-400 μg/ml) that significantly reduce spontaneous neuronal firing of VTA DA neurons via a GABA - but not GABA -mediated mechanism, suppressed the stimulatory actions of both morphine and ethanol. Moreover, administration of WSE at a dose (75 mg/kg) that fails to affect basal DA transmission, significantly prevented both morphine- and ethanol-elicited increases of DA in the AcbSh. Overall, these results highlight the ability of WSE to interfere with morphine- and ethanol-mediated central effects and suggest a mechanistic interpretation of the efficacy of this extract to prevent the motivational properties of these compounds.

• Publisher: Frontiers Research Foundation,Frontiers Media S.A
• Subject: Brain research / Brain slice preparation / Dopamine / Dopamine receptors / Drug addiction / Drug self-administration / Ethanol / Firing rate / Mesolimbic system / Microdialysis / Morphine / Narcotics / Neurons / Neuroscience / Neurosciences / Nucleus accumbens / nucleus accumbens shell / Place preference conditioning / Rodents / standardized Withania somnifera extract / ventral tegmental area / Ventral tegmentum / Withania somnifera / γ-Aminobutyric acid A receptors / γ-Aminobutyric acid B receptors