Sardinian alcohol non-preferring (sNP) rats carry a point mutation (R100Q) in the cerebellar expressed GABAA receptor α6 subunit gene, leading to a higher sensitivity to ethanol and diazepam. The role of the α6 subunit gene cluster in the ethanol non-preferring phenotype was here investigated by measuring the levels of α1, α6 and γ2 peptide in the cerebellum of normal (RR) and mutated (QQ) sNP rats after 2 weeks of chronic ethanol administration. Western blot analysis revealed that the α6 subunit is increased in RR sNP rats after chronic ethanol exposure (25.44%±8.69 versus control), while it remained unchanged in mutated QQ sNP rats. Interestingly, chronic ethanol administration decreased α1 peptide levels in the cerebellum of both rat lines to a similar extent (30.99%±6.74 and 27.12%±9.83 in RR and QQ rats, respectively), while γ2 peptide levels remained unchanged. To further correlate the genetic and biochemical difference of the normal and mutated sNP rats with their aversive phenotype, we exposed sNP rats to a protocol of acquisition and maintenance of ethanol drinking. QQ sNP rats drank less ethanol than RR rats during the acquisition phase, but such difference was lost during the maintenance phase. These data may contribute to elucidating the mechanisms of alcohol avoidance in rat lines selected for this behavior when exposed to ethanol solution. © 2003 Elsevier B.V. All rights reserved.
The cerebellar GABAA α6 subunit is differentially modulated by chronic ethanol exposure in normal (R100R) and mutated (Q100Q) sNP rats / Sanna, A; Congeddu, E; Saba, L; Porcella, A; Marchese, G; Ruiu, S; Casti, P; Saba, P; Pani, L.. - In: BRAIN RESEARCH. - ISSN 1872-6240. - 998:2(2004), pp. 148-154. [10.1016/j.brainres.2003.11.013]
The cerebellar GABAA α6 subunit is differentially modulated by chronic ethanol exposure in normal (R100R) and mutated (Q100Q) sNP rats
Pani, L.
2004
Abstract
Sardinian alcohol non-preferring (sNP) rats carry a point mutation (R100Q) in the cerebellar expressed GABAA receptor α6 subunit gene, leading to a higher sensitivity to ethanol and diazepam. The role of the α6 subunit gene cluster in the ethanol non-preferring phenotype was here investigated by measuring the levels of α1, α6 and γ2 peptide in the cerebellum of normal (RR) and mutated (QQ) sNP rats after 2 weeks of chronic ethanol administration. Western blot analysis revealed that the α6 subunit is increased in RR sNP rats after chronic ethanol exposure (25.44%±8.69 versus control), while it remained unchanged in mutated QQ sNP rats. Interestingly, chronic ethanol administration decreased α1 peptide levels in the cerebellum of both rat lines to a similar extent (30.99%±6.74 and 27.12%±9.83 in RR and QQ rats, respectively), while γ2 peptide levels remained unchanged. To further correlate the genetic and biochemical difference of the normal and mutated sNP rats with their aversive phenotype, we exposed sNP rats to a protocol of acquisition and maintenance of ethanol drinking. QQ sNP rats drank less ethanol than RR rats during the acquisition phase, but such difference was lost during the maintenance phase. These data may contribute to elucidating the mechanisms of alcohol avoidance in rat lines selected for this behavior when exposed to ethanol solution. © 2003 Elsevier B.V. All rights reserved.
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