TY - JOUR
T1 - Glucocorticoid and polyamine interactions in the plasticity of glutamatergic synapses that contribute to ethanol-associated dependence and neuronal injury
AU - Prendergast, Mark A.
AU - Mulholland, Patrick J.
PY - 2012/3
Y1 - 2012/3
N2 - Stress contributes to the development of ethanol dependence and is also a consequence of dependence. However, the complexity of physiological interactions between activation of the hypothalamic-pituitary-adrenal (HPA) axis and ethanol itself is not well delineated. Emerging evidence derived from examination of corticotropin-releasing factor systems and glucocorticoid receptor systems in ethanol dependence suggests a role for pharmacological manipulation of the HPA axis in attenuating ethanol intake, though it is not clear how activation of the HPA axis may promote ethanol dependence or contribute to the neuroadaptative changes that accompany the development of dependence and the severity of ethanol withdrawal. This review examines the role that glucocorticoids, in particular, have in promoting ethanol-associated plasticity of glutamatergic synapses by influencing expression of endogenous linear polyamines and polyamine-sensitive polypeptide subunits of N-methyl-D-aspartate (NMDA)-type glutamate receptors. We provide evidence that interactions among glucocorticoid systems, polyamines and NMDA receptors are highly relevant to both the development of ethanol dependence and to behavioral and neuropathological sequelae associated with ethanol withdrawal. Examination of these issues is likely to be of critical importance not only in further elucidating the neurobiology of HPA axis dysregulation in ethanol dependence, but also with regard to identification of novel therapeutic targets that may be exploited in the treatment of ethanol dependence.
AB - Stress contributes to the development of ethanol dependence and is also a consequence of dependence. However, the complexity of physiological interactions between activation of the hypothalamic-pituitary-adrenal (HPA) axis and ethanol itself is not well delineated. Emerging evidence derived from examination of corticotropin-releasing factor systems and glucocorticoid receptor systems in ethanol dependence suggests a role for pharmacological manipulation of the HPA axis in attenuating ethanol intake, though it is not clear how activation of the HPA axis may promote ethanol dependence or contribute to the neuroadaptative changes that accompany the development of dependence and the severity of ethanol withdrawal. This review examines the role that glucocorticoids, in particular, have in promoting ethanol-associated plasticity of glutamatergic synapses by influencing expression of endogenous linear polyamines and polyamine-sensitive polypeptide subunits of N-methyl-D-aspartate (NMDA)-type glutamate receptors. We provide evidence that interactions among glucocorticoid systems, polyamines and NMDA receptors are highly relevant to both the development of ethanol dependence and to behavioral and neuropathological sequelae associated with ethanol withdrawal. Examination of these issues is likely to be of critical importance not only in further elucidating the neurobiology of HPA axis dysregulation in ethanol dependence, but also with regard to identification of novel therapeutic targets that may be exploited in the treatment of ethanol dependence.
KW - Alcoholism
KW - NMDA receptors
KW - glucocorticoids
KW - neuropathology
KW - polyamines
KW - stress
UR - http://www.scopus.com/inward/record.url?scp=84857658496&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84857658496&partnerID=8YFLogxK
U2 - 10.1111/j.1369-1600.2011.00375.x
DO - 10.1111/j.1369-1600.2011.00375.x
M3 - Review article
C2 - 21967628
AN - SCOPUS:84857658496
SN - 1355-6215
VL - 17
SP - 209
EP - 223
JO - Addiction Biology
JF - Addiction Biology
IS - 2
ER -