title: Glucocorticoid and polyamine interactions in the plasticity of glutamatergic synapses that contribute to ethanol-associated dependence and neuronal injury.
abstract: 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.
authors.affiliation: Department of Psychology and Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Prendergast
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Mulholland
mesh_terms: D020268:Alcohol-Induced Disorders, Nervous System / Q000209:etiology*; D000437:Alcoholism / Q000209:etiology* / Q000378:metabolism; D000818:Animals; D002492:Central Nervous System Depressants / Q000009:adverse effects; D000431:Ethanol / Q000009:adverse effects; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000187:drug effects; D011073:Polyamines / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D012377:Rodentia; D013315:Stress, Psychological / Q000378:metabolism; D013569:Synapses / Q000187:drug effects*; D015854:Up-Regulation
chemical_list: D002492:Central Nervous System Depressants; D005938:Glucocorticoids; D011073:Polyamines; D011965:Receptors, Glucocorticoid; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol