TY - JOUR
T1 - The glucocorticoid analog dexamethasone alters the expression and the distribution of dopamine receptors and enkephalin within cortico-subcortical regions
AU - Iasevoli, Felice
AU - Aloj, Luigi
AU - Latte, Gianmarco
AU - Avvisati, Livia
AU - Marmo, Federica
AU - Tomasetti, Carmine
AU - Buonaguro, Elisabetta F.
AU - Simeoli, Chiara
AU - Pivonello, Rosario
AU - Colao, Annamaria
AU - de Bartolomeis, Andrea
PY - 2013
Y1 - 2013
N2 - In humans, glucocorticoid excess may cause neuropsychiatric symptoms, including psychosis and cognitive impairment, and glucocorticoid signaling hyperactivation may sensitize to substance of abuse. The aim of this work was to evaluate whether exposure to glucocorticoid excess triggers molecular changes in dopaminergic and opioidergic systems within relevant forebrain areas. We acutely exposed Sprague-Dawley rats to dexamethasone, a glucocorticoid analog, or vehicle and evaluated the mRNA expression of dopamine D1 and D2 receptors and enkephalin within the cortex, the striatum, and the midbrain. Dexamethasone reduced mRNA expression of D1 receptor and enkephalin in the cortex. In the striatum, dexamethasone reduced the expression of D1 receptor mRNA, but not that of D2 receptor and enkephalin. No significant changes in D2 receptor mRNA expression were observed in the midbrain. Basal distribution of D1 and D2 receptor mRNA showed a clear-cut striatal/cortical gradient, while this distribution was less obvious for enkephalin mRNA. Dexamethasone increased the cortico-striatal separation in terms of D1 and D2 receptor mRNA expression. These molecular changes may represent adaptive mechanisms to dexamethasone-induced potentiation of dopaminergic and opioidergic transmission, mostly in cortical areas.
AB - In humans, glucocorticoid excess may cause neuropsychiatric symptoms, including psychosis and cognitive impairment, and glucocorticoid signaling hyperactivation may sensitize to substance of abuse. The aim of this work was to evaluate whether exposure to glucocorticoid excess triggers molecular changes in dopaminergic and opioidergic systems within relevant forebrain areas. We acutely exposed Sprague-Dawley rats to dexamethasone, a glucocorticoid analog, or vehicle and evaluated the mRNA expression of dopamine D1 and D2 receptors and enkephalin within the cortex, the striatum, and the midbrain. Dexamethasone reduced mRNA expression of D1 receptor and enkephalin in the cortex. In the striatum, dexamethasone reduced the expression of D1 receptor mRNA, but not that of D2 receptor and enkephalin. No significant changes in D2 receptor mRNA expression were observed in the midbrain. Basal distribution of D1 and D2 receptor mRNA showed a clear-cut striatal/cortical gradient, while this distribution was less obvious for enkephalin mRNA. Dexamethasone increased the cortico-striatal separation in terms of D1 and D2 receptor mRNA expression. These molecular changes may represent adaptive mechanisms to dexamethasone-induced potentiation of dopaminergic and opioidergic transmission, mostly in cortical areas.
KW - Cognition
KW - Cortex
KW - Cortisol
KW - Dexamethasone
KW - Gene expression
KW - Glucocorticoid
KW - Schizophrenia
KW - Striatum
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UR - http://www.scopus.com/inward/citedby.url?scp=84901247672&partnerID=8YFLogxK
U2 - 10.2174/187446720603140415215941
DO - 10.2174/187446720603140415215941
M3 - Article
C2 - 23862670
AN - SCOPUS:84901247672
VL - 6
SP - 149
EP - 155
JO - Current Molecular Pharmacology
JF - Current Molecular Pharmacology
SN - 1874-4702
IS - 3
ER -