Corticosterone enhances N-methyl-D-aspartate receptor signaling to promote isolated ventral tegmental area activity in a reconstituted mesolimbic dopamine pathway.

Corticosterone enhances N-methyl-D-aspartate receptor signaling to promote isolated ventral tegmental area activity in a reconstituted mesolimbic dopamine pathway. Brain Res Bull. 2015 Nov 26; Authors: Berry JN, Saunders MA, Sharrett-Field LJ, Reynolds AR, Bardo MT, Pauly JR, Prendergast MA Abstract Elevations in circulating corticosteroids during periods of stress may influence activity of the mesolimbic dopamine reward pathway by increasing glutamatergic N- methyl-D-aspartate (NMDA) receptor expression and/or function in a glucocorticoid receptor-dependent manner. The current study employed organotypic co-cultures of the ventral tegmental area (VTA) and nucleus accumbens (NAcc) to examine the effects of corticosterone exposure on NMDA receptor-mediated neuronal viability. Co-cultures were pre-exposed to vehicle or corticosterone (CORT; 1μM) for 5 days prior to a 24hour co-exposure to NMDA (200μM). Co-cultures pre-exposed to a non-toxic concentration of corticosterone and subsequently NMDA showed significant neurotoxicity in the VTA only. This was evidenced by increases in propidium iodide uptake as well as decreases in immunoreactivity of the neuronal nuclear protein (NeuN). Co-exposure to the NMDA receptor antagonist 2-amino-7-phosphonovaleric acid (APV; 50μM) or the glucocorticoid receptor (GR) antagonist mifepristone (10μM) attenuated neurotoxicity. In contrast, the combination of corticosterone and NMDA did not produce any ...
Source: Brain Research Bulletin - Category: Neurology Authors: Tags: Brain Res Bull Source Type: research