http://www.cnr.it/ontology/cnr/individuo/prodotto/ID182914

Neurosteroids, GABAA receptors, and ethanol dependence. (Articolo in rivista)

Type

Articolo in rivista (Classe)
Prodotto della ricerca (Classe)

Label

Neurosteroids, GABAA receptors, and ethanol dependence. (Articolo in rivista) (literal)

Anno

2006-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

10.1007/s00213-005-0126-0 (literal)

Alternative label

FOLLESA P; BIGGIO F; TALANI G; MURRU L; SERRA M; SANNA E; BIGGIO G (2006)
Neurosteroids, GABAA receptors, and ethanol dependence.
in Psychopharmacologia
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

FOLLESA P; BIGGIO F; TALANI G; MURRU L; SERRA M; SANNA E; BIGGIO G (literal)

Pagina inizio

267 (literal)

Pagina fine

280 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url

http://www.springerlink.com/content/hj3126807876t240/?MUD=MP (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

186 (literal)

Rivista

Psychopharmacologia (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali

14 (literal)

Note

PubMe (literal)
ISI Web of Science (WOS) (literal)
Scopu (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

Department of Experimental Biology \"Bernardo Loddo\", University of Cagliari, Center of Excellence for the Neurobiology of Dependence, University of Cagliari CNR Institute of Neuroscience (literal)

Titolo

Neurosteroids, GABAA receptors, and ethanol dependence. (literal)

Abstract

Rationale: Changes in the expression of type A receptors for ?-aminobutyric acid (GABA) represent one of the mechanisms implicated in the development of tolerance to and dependence on ethanol. The impact of such changes on the function and pharmacological sensitivity of GABAA receptors (GABAARs) has remained unclear, however. Certain behavioral and electrophysiological actions of ethanol are mediated by an increase in the concentration of neuroactive steroids in the brain that results from stimulation of the hypothalamic-pituitary-adrenal (HPA) axis. Such steroids include potent modulators of GABAAR function. Objectives: We have investigated the effect of ethanol exposure and withdrawal on subunit expression and receptor function evaluated by subunit selective compounds, as well as the effects of short-term exposure to ethanol on both neurosteroid synthesis and GABA AR function, in isolated neurons and brain tissue. Results: Chronic treatment with and subsequent withdrawal from ethanol alter the expression of genes for specific GABAAR subunits in cultured rat neurons, and these changes are associated with alterations in receptor function and pharmacological sensitivity to neurosteroids, zaleplon, and flumazenil. Acute ethanol exposure increases the amount of 3?-hydroxy-5?-pregnan-20- one (allopregnanolone) in hippocampal slices by a local action independent of the activity of the HPA axis. This effect of ethanol was associated with an increased amplitude of GABAAR-mediated miniature inhibitory postsynaptic currents recorded from CA1 pyramidal neurons in such slices. Conclusions: Chronic ethanol exposure elicits changes in the subunit composition of GABAARs, which, in turn, likely contribute to changes in receptor function associated with the altered pharmacological and behavioral sensitivity characteristic of ethanol tolerance and dependence. Ethanol may also modulate GABAAR function by increasing the de novo synthesis of neurosteroids in the brain in a manner independent of the HPA axis. This latter mechanism may play an important role in the central effects of ethanol. (literal)

Prodotto di