Various lines of evidence suggest a functional interaction between GABA(A) and Neuropeptide Y (NPY)-Y-1 receptor (Y1R) mediated transmissions in various brain regions, which can be important in the regulation of sedation, feeding, anxious behaviour and neuronal excitability. By using a transgenic, mouse model carrying the murine Y1R gene promoter fused to the lacZ reporter gene (Y1R/LacZ mice), we showed that prolonged pharmacologically or physiologically induced changes in the cerebrocortical concentrations of the neuroactive steroids 3alpha-hydroxy5alpha-pregnan-20-one (3alpha,5alpha TH PROG) and tetrahydrodeoxycorticosterone (3alpha,5alpha TH DOC) increases Y1R/LacZ transgene expression in the central and medial amygdala, an effect similar to that induced by long-term treatment with positive modulators of the GABAA receptor complex (diazepam or abecarnil). We also demonstrated that fluctuations in the cerebrocortical concentrations of 3alpha, 5alpha-TH PROG and 3alpha,5alpha TH DOC during voluntary ethanol consumption and ethanol withdrawal induces a marked increase in Y1R gene expression that becomes apparent 48 h after withdrawal. These data provide evidence that neuroactive steroids may play an important role in the functional interaction between the GABA(A) receptor and NPY-Y1R mediated pathways in the amygdala, which might represent an important regulatory mechanism for modulation of several functions, including ethanol withdrawal. (c) 2006 Elsevier Inc. All rights reserved.

Role of brain neuroactive steroids in the functional interplay between the GABA(A) and the NPY-Y-1 receptor mediated signals in the amygdala

SERRA, MARIANGELA;
2006-01-01

Abstract

Various lines of evidence suggest a functional interaction between GABA(A) and Neuropeptide Y (NPY)-Y-1 receptor (Y1R) mediated transmissions in various brain regions, which can be important in the regulation of sedation, feeding, anxious behaviour and neuronal excitability. By using a transgenic, mouse model carrying the murine Y1R gene promoter fused to the lacZ reporter gene (Y1R/LacZ mice), we showed that prolonged pharmacologically or physiologically induced changes in the cerebrocortical concentrations of the neuroactive steroids 3alpha-hydroxy5alpha-pregnan-20-one (3alpha,5alpha TH PROG) and tetrahydrodeoxycorticosterone (3alpha,5alpha TH DOC) increases Y1R/LacZ transgene expression in the central and medial amygdala, an effect similar to that induced by long-term treatment with positive modulators of the GABAA receptor complex (diazepam or abecarnil). We also demonstrated that fluctuations in the cerebrocortical concentrations of 3alpha, 5alpha-TH PROG and 3alpha,5alpha TH DOC during voluntary ethanol consumption and ethanol withdrawal induces a marked increase in Y1R gene expression that becomes apparent 48 h after withdrawal. These data provide evidence that neuroactive steroids may play an important role in the functional interaction between the GABA(A) receptor and NPY-Y1R mediated pathways in the amygdala, which might represent an important regulatory mechanism for modulation of several functions, including ethanol withdrawal. (c) 2006 Elsevier Inc. All rights reserved.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11584/39803
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