GABA and neuropeptide Y (NPY) are functionally coupled in the amygdala and may interact in the regulation of sedation, feeding and anxious behaviour. By using Y1R/LacZ transgenic mice harbouring the murine Y1 receptor (Y1R) gene promoter fused to a lacZ gene, we showed that the sustained increase in the brain concentrations of the neuroactive steroid allopregnanolone (AP) induced by pharmacological treatment or by physiological conditions might modulate both GABAA and Y1R gene expression. The interaction between GABA and NPY might also play a role in the regulation of ethanol consumption and withdrawal. To investigate whether long-lasting changes in the brain concentrations of neuroactive steroids produced in response to ethanol consumption might also affect Y1 receptor expression, we studied the effect of voluntary alcohol consumption and withdrawal on cerebrocortical concentrations of AP and Y1R/LacZ gene expression in the amygdala. At this purpose Y1R/LacZ mice were habituated to drinking increasing concentrations of ethanol (3, 6, 10, 20%, v/v) by using a two-bottles-choice procedure and killed or withdrawn for 24-h and 48-h after 4 weeks. We also studied the effect of the treatment with gamma-hydroxy-butirate (GHB) (150-600 mg/Kg i.p.), a GABA analogue effective in the therapy of alcohol dependence on the same parameters. Voluntary alcohol consumption increased the cerebrocortical concentrations of AP but failed to modify Y1R/LacZ transgene expression in the central and medial amygdala. Conversely the decrease of AP concentrations induced by ethanol withdrawal is associated with an increase in the Y1R/LacZ transgene expression The treatment with GHB, that increased the brain concentrations of AP, induced an increase of NPY immunoreactivity and a concomitant decrease of Y1R/LacZ expression in the amygdala. These data suggest that the decrease in NPY-Y1R mediated transmission contribute to the development of ethanol withdrawal symptoms and that NPY represent one of the targets of the pharmacological action of GHB. We are investigating whether changes in brain concentrations of AP and Y1R gene expression in response to ethanol withdrawal or GHB treatment are functionally associated.
Voluntary alcohol consumption and gamma-hydroxy-butirate (Ghb)
MELE, PAOLO;EVA, Carola Eugenia
2005-01-01
Abstract
GABA and neuropeptide Y (NPY) are functionally coupled in the amygdala and may interact in the regulation of sedation, feeding and anxious behaviour. By using Y1R/LacZ transgenic mice harbouring the murine Y1 receptor (Y1R) gene promoter fused to a lacZ gene, we showed that the sustained increase in the brain concentrations of the neuroactive steroid allopregnanolone (AP) induced by pharmacological treatment or by physiological conditions might modulate both GABAA and Y1R gene expression. The interaction between GABA and NPY might also play a role in the regulation of ethanol consumption and withdrawal. To investigate whether long-lasting changes in the brain concentrations of neuroactive steroids produced in response to ethanol consumption might also affect Y1 receptor expression, we studied the effect of voluntary alcohol consumption and withdrawal on cerebrocortical concentrations of AP and Y1R/LacZ gene expression in the amygdala. At this purpose Y1R/LacZ mice were habituated to drinking increasing concentrations of ethanol (3, 6, 10, 20%, v/v) by using a two-bottles-choice procedure and killed or withdrawn for 24-h and 48-h after 4 weeks. We also studied the effect of the treatment with gamma-hydroxy-butirate (GHB) (150-600 mg/Kg i.p.), a GABA analogue effective in the therapy of alcohol dependence on the same parameters. Voluntary alcohol consumption increased the cerebrocortical concentrations of AP but failed to modify Y1R/LacZ transgene expression in the central and medial amygdala. Conversely the decrease of AP concentrations induced by ethanol withdrawal is associated with an increase in the Y1R/LacZ transgene expression The treatment with GHB, that increased the brain concentrations of AP, induced an increase of NPY immunoreactivity and a concomitant decrease of Y1R/LacZ expression in the amygdala. These data suggest that the decrease in NPY-Y1R mediated transmission contribute to the development of ethanol withdrawal symptoms and that NPY represent one of the targets of the pharmacological action of GHB. We are investigating whether changes in brain concentrations of AP and Y1R gene expression in response to ethanol withdrawal or GHB treatment are functionally associated.
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