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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

Spontaneous locomotor activity in isolated (SI) and group-housed (GH) C57BL/6J mice. Locomotor activity was assessed in a motility meter after the 6-week isolation period. The different parameters of motor activity (A) total distance traveled, (B) locomotion time, (C) rest time, and (D) horizontal activity, were averaged in bins of 5 min, for 60 continuous min. Data in graphs (A) through (D) are mean ± SEM (n = 9 per group) of the absolute values of the different measures. Graph (E) summarizes the effects of SI on locomotor activity as measured during the initial 15 min. Data are expressed as mean ± SEM of the percentage vs. GH mice. *p < 0.05 vs. GH animals.
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Figure 1: Spontaneous locomotor activity in isolated (SI) and group-housed (GH) C57BL/6J mice. Locomotor activity was assessed in a motility meter after the 6-week isolation period. The different parameters of motor activity (A) total distance traveled, (B) locomotion time, (C) rest time, and (D) horizontal activity, were averaged in bins of 5 min, for 60 continuous min. Data in graphs (A) through (D) are mean ± SEM (n = 9 per group) of the absolute values of the different measures. Graph (E) summarizes the effects of SI on locomotor activity as measured during the initial 15 min. Data are expressed as mean ± SEM of the percentage vs. GH mice. *p < 0.05 vs. GH animals.

Mentions: At the end of the isolation period, both GH and SI mice were tested for their spontaneous locomotor activity in a motility meter for 60 min. The data indicate that SI was associated with a reduced locomotor activity compared to animals reared in group. In fact, in SI mice there was a significant decrease in total distance traveled, locomotion time, horizontal activity, and a parallel increase in rest time, compared to GH animals (Figure 1, p < 0.05).


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)

Spontaneous locomotor activity in isolated (SI) and group-housed (GH) C57BL/6J mice. Locomotor activity was assessed in a motility meter after the 6-week isolation period. The different parameters of motor activity (A) total distance traveled, (B) locomotion time, (C) rest time, and (D) horizontal activity, were averaged in bins of 5 min, for 60 continuous min. Data in graphs (A) through (D) are mean ± SEM (n = 9 per group) of the absolute values of the different measures. Graph (E) summarizes the effects of SI on locomotor activity as measured during the initial 15 min. Data are expressed as mean ± SEM of the percentage vs. GH mice. *p < 0.05 vs. GH animals.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Spontaneous locomotor activity in isolated (SI) and group-housed (GH) C57BL/6J mice. Locomotor activity was assessed in a motility meter after the 6-week isolation period. The different parameters of motor activity (A) total distance traveled, (B) locomotion time, (C) rest time, and (D) horizontal activity, were averaged in bins of 5 min, for 60 continuous min. Data in graphs (A) through (D) are mean ± SEM (n = 9 per group) of the absolute values of the different measures. Graph (E) summarizes the effects of SI on locomotor activity as measured during the initial 15 min. Data are expressed as mean ± SEM of the percentage vs. GH mice. *p < 0.05 vs. GH animals.
Mentions: At the end of the isolation period, both GH and SI mice were tested for their spontaneous locomotor activity in a motility meter for 60 min. The data indicate that SI was associated with a reduced locomotor activity compared to animals reared in group. In fact, in SI mice there was a significant decrease in total distance traveled, locomotion time, horizontal activity, and a parallel increase in rest time, compared to GH animals (Figure 1, p < 0.05).

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