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Voluntary Ethanol Consumption Induced by Social Isolation Reverses the Increase of α(4)/δ GABA(A) Receptor Gene Expression and Function in the Hippocampus of C57BL/6J Mice.

Sanna E, Talani G, Obili N, Mascia MP, Mostallino MC, Secci PP, Pisu MG, Biggio F, Utzeri C, Olla P, Biggio G, Follesa P - Front Neurosci (2011)

Bottom Line: SI stress induced a marked reduction in hippocampal 3α-hydroxy-5α-pregnan-20-one (3α,5α-TH PROG) and was associated with molecular and functional changes of the GABA(A)R.Nevertheless, the increase in EtOH consumption did not restore the reduction in hippocampal 3α,5α-TH PROG induced by SI.We conclude that self-administration of EtOH selectively abolishes the increase of α(4) subunit but not other neurochemical, molecular, and functional modifications induced by SI prolonged mild stress.

View Article: PubMed Central - PubMed

Affiliation: Section of Neuroscience, Department of Experimental Biology, Center of Excellence for the Neurobiology of Dependence, University of Cagliari Monserrato, Cagliari, Italy.

ABSTRACT
Post-weaning social isolation (SI) is a model of prolonged mild stress characterized by behavioral and neurochemical alterations. We used SI in C57BL/6J mice to investigate the effects of ethanol (EtOH) in the free-choice drinking paradigm on gene expression and function of γ-aminobutyric acid type A receptors (GABA(A)Rs) and the role of neuroactive steroids in the actions of EtOH in the hippocampus. SI stress induced a marked reduction in hippocampal 3α-hydroxy-5α-pregnan-20-one (3α,5α-TH PROG) and was associated with molecular and functional changes of the GABA(A)R. The gene expression of the α(4) and δ subunits was increased in the hippocampus of SI C57BL/6J mice; the expression of the γ(2) subunit was decreased whereas that of the α(1) did not change. Patch-clamp recordings in dentate gyrus (DG) granule cells obtained from SI C57BL/6J mice revealed a greater enhancement of tonic currents induced by α-(4,5,6,7-tetrahydroisoxazolo[5,4-c] pyridin-3-ol (THIP) compared to that in control C57BL/6J mice. These neurochemical, molecular and functional changes observed in SI C57BL/6J mice were associated with an increased EtOH intake and EtOH preference. Nevertheless, the increase in EtOH consumption did not restore the reduction in hippocampal 3α,5α-TH PROG induced by SI. EtOH self-administration blocked the changes in gene expression of the α(4) subunit but not those of the δ and γ(2) subunits induced by SI. In addition, EtOH self-administration did not block the SI-induced changes in GABA(A)R-mediated tonic inhibition in hippocampal granule cells but increased the frequency of basal GABAergic sIPSCs in DG granule cells. We conclude that self-administration of EtOH selectively abolishes the increase of α(4) subunit but not other neurochemical, molecular, and functional modifications induced by SI prolonged mild stress.

No MeSH data available.


Related in: MedlinePlus

Effect of voluntary EtOH consumption on the concentration of 3α,5α-TH PROG in the hippocampus of group-housed (GH) and socially isolated (SI) C57BL/6J mice. Animals were housed in groups or in isolation for 6 weeks with free access for 2 h a day to EtOH or water as described in the Section “Materials and Methods.” The last day of isolation animals were sacrificed at the end of the 2-h EtOH access session and the hippocampal concentration of 3α,5α-TH PROG was measured. Data are mean ± SEM (n = 9 per group): Two-way analysis of variance (ANOVA) followed by Newman–Keuls post hoc test; *p < 0.01 vs. corresponding GH animals as indicated.
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Figure 3: Effect of voluntary EtOH consumption on the concentration of 3α,5α-TH PROG in the hippocampus of group-housed (GH) and socially isolated (SI) C57BL/6J mice. Animals were housed in groups or in isolation for 6 weeks with free access for 2 h a day to EtOH or water as described in the Section “Materials and Methods.” The last day of isolation animals were sacrificed at the end of the 2-h EtOH access session and the hippocampal concentration of 3α,5α-TH PROG was measured. Data are mean ± SEM (n = 9 per group): Two-way analysis of variance (ANOVA) followed by Newman–Keuls post hoc test; *p < 0.01 vs. corresponding GH animals as indicated.

Mentions: In order to test the hypothesis that increased drinking behavior and EtOH preference induced by SI could restore the concentrations of neuroactive steroids to steady state levels in the hippocampus we measured 3α,5α-TH PROG in both GH and SI mice that had free access to EtOH or water. All measurements were done at the end of the 2-h session the last day of SI. Consistent with our previous data in the rat (Serra et al., 2000), SI of C57BL/6J mice induced a significant decreases in hippocampal concentrations of 3α,5α-TH PROG compared to GH mice (Figure 3; p < 0.05). Voluntary EtOH consumption throughout the SI period for just 2 h at day did not restore the steady state levels of 3α,5α-TH PROG which remained as low as those measured in SI mice that drank water (Figure 3).


Voluntary Ethanol Consumption Induced by Social Isolation Reverses the Increase of α(4)/δ GABA(A) Receptor Gene Expression and Function in the Hippocampus of C57BL/6J Mice.

Sanna E, Talani G, Obili N, Mascia MP, Mostallino MC, Secci PP, Pisu MG, Biggio F, Utzeri C, Olla P, Biggio G, Follesa P - Front Neurosci (2011)

Effect of voluntary EtOH consumption on the concentration of 3α,5α-TH PROG in the hippocampus of group-housed (GH) and socially isolated (SI) C57BL/6J mice. Animals were housed in groups or in isolation for 6 weeks with free access for 2 h a day to EtOH or water as described in the Section “Materials and Methods.” The last day of isolation animals were sacrificed at the end of the 2-h EtOH access session and the hippocampal concentration of 3α,5α-TH PROG was measured. Data are mean ± SEM (n = 9 per group): Two-way analysis of variance (ANOVA) followed by Newman–Keuls post hoc test; *p < 0.01 vs. corresponding GH animals as indicated.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3039156&req=5

Figure 3: Effect of voluntary EtOH consumption on the concentration of 3α,5α-TH PROG in the hippocampus of group-housed (GH) and socially isolated (SI) C57BL/6J mice. Animals were housed in groups or in isolation for 6 weeks with free access for 2 h a day to EtOH or water as described in the Section “Materials and Methods.” The last day of isolation animals were sacrificed at the end of the 2-h EtOH access session and the hippocampal concentration of 3α,5α-TH PROG was measured. Data are mean ± SEM (n = 9 per group): Two-way analysis of variance (ANOVA) followed by Newman–Keuls post hoc test; *p < 0.01 vs. corresponding GH animals as indicated.
Mentions: In order to test the hypothesis that increased drinking behavior and EtOH preference induced by SI could restore the concentrations of neuroactive steroids to steady state levels in the hippocampus we measured 3α,5α-TH PROG in both GH and SI mice that had free access to EtOH or water. All measurements were done at the end of the 2-h session the last day of SI. Consistent with our previous data in the rat (Serra et al., 2000), SI of C57BL/6J mice induced a significant decreases in hippocampal concentrations of 3α,5α-TH PROG compared to GH mice (Figure 3; p < 0.05). Voluntary EtOH consumption throughout the SI period for just 2 h at day did not restore the steady state levels of 3α,5α-TH PROG which remained as low as those measured in SI mice that drank water (Figure 3).

Bottom Line: SI stress induced a marked reduction in hippocampal 3α-hydroxy-5α-pregnan-20-one (3α,5α-TH PROG) and was associated with molecular and functional changes of the GABA(A)R.Nevertheless, the increase in EtOH consumption did not restore the reduction in hippocampal 3α,5α-TH PROG induced by SI.We conclude that self-administration of EtOH selectively abolishes the increase of α(4) subunit but not other neurochemical, molecular, and functional modifications induced by SI prolonged mild stress.

View Article: PubMed Central - PubMed

Affiliation: Section of Neuroscience, Department of Experimental Biology, Center of Excellence for the Neurobiology of Dependence, University of Cagliari Monserrato, Cagliari, Italy.

ABSTRACT
Post-weaning social isolation (SI) is a model of prolonged mild stress characterized by behavioral and neurochemical alterations. We used SI in C57BL/6J mice to investigate the effects of ethanol (EtOH) in the free-choice drinking paradigm on gene expression and function of γ-aminobutyric acid type A receptors (GABA(A)Rs) and the role of neuroactive steroids in the actions of EtOH in the hippocampus. SI stress induced a marked reduction in hippocampal 3α-hydroxy-5α-pregnan-20-one (3α,5α-TH PROG) and was associated with molecular and functional changes of the GABA(A)R. The gene expression of the α(4) and δ subunits was increased in the hippocampus of SI C57BL/6J mice; the expression of the γ(2) subunit was decreased whereas that of the α(1) did not change. Patch-clamp recordings in dentate gyrus (DG) granule cells obtained from SI C57BL/6J mice revealed a greater enhancement of tonic currents induced by α-(4,5,6,7-tetrahydroisoxazolo[5,4-c] pyridin-3-ol (THIP) compared to that in control C57BL/6J mice. These neurochemical, molecular and functional changes observed in SI C57BL/6J mice were associated with an increased EtOH intake and EtOH preference. Nevertheless, the increase in EtOH consumption did not restore the reduction in hippocampal 3α,5α-TH PROG induced by SI. EtOH self-administration blocked the changes in gene expression of the α(4) subunit but not those of the δ and γ(2) subunits induced by SI. In addition, EtOH self-administration did not block the SI-induced changes in GABA(A)R-mediated tonic inhibition in hippocampal granule cells but increased the frequency of basal GABAergic sIPSCs in DG granule cells. We conclude that self-administration of EtOH selectively abolishes the increase of α(4) subunit but not other neurochemical, molecular, and functional modifications induced by SI prolonged mild stress.

No MeSH data available.


Related in: MedlinePlus