A transcriptional study in mice with different ethanol-drinking profiles: Possible involvement of the GABA_B receptor

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• 作者：Andrea Frozino Ribeiro ; Diego Correia ; Adriana Amorim Torres ; Gustavo Roberto Villas Boas ; Andr¨¦ Veloso Lima Rueda ; Rosana Camarini ; Silvana Chiavegatto ; Roseli Boerngen-Lacerda ; Ana L¨²cia Brunialti-Godard
• 关键词：Behavioral genetics ; mRNA ; Ethanol consumption ; Addicted ; GABAB receptor ; Mice
• 刊名：Pharmacology Biochemistry and Behavior
• 出版年：2012
• 出版时间：August, 2012
• 年：2012
• 卷：102
• 期：2
• 页码：224-232
• 全文大小：472 K

文摘

Previous studies have suggested that ¦Ã-aminobutyric acid-B (GABA_B) receptor agonists effectively reduce ethanol intake. The quantification using real-time polymerase chain reaction of Gabbr1 and Gabbr2 mRNA from the prefrontal cortex, hypothalamus, hippocampus, and striatum in mice exposed to an animal model of the addiction developed in our laboratory was performed to evaluate the involvement of the GABA_B receptor in ethanol consumption. We used outbred, Swiss mice exposed to a three-bottle free-choice model (water, 5 % v/v ethanol, and 10 % v/v ethanol) that consisted of four phases: acquisition (AC), withdrawal (W), reexposure (RE), and quinine-adulteration (AD). Based on individual ethanol intake, the mice were classified into three groups: ¡°addicted¡± (A group; preference for ethanol and persistent consumption during all phases), ¡°heavy¡± (H group; preference for ethanol and a reduction in ethanol intake in the AD phase compared to AC phase), and ¡°light¡± (L group; preference for water during all phases). In the prefrontal cortex in the A group, we found high Gabbr1 and Gabbr2 transcription levels, with significantly higher Gabbr1 transcription levels compared with the C (ethanol-naive control mice), L, and H groups. In the hippocampus in the A group, Gabbr2 mRNA levels were significantly lower compared with the C, L, and H groups. In the striatum, we found a significant increase in Gabbr1 transcription levels compared with the C, L, and H groups. No differences in Gabbr1 or Gabbr2 transcription levels were observed in the hypothalamus among groups. In summary, Gabbr1 and Gabbr2 transcription levels were altered in cerebral areas related to drug taking only in mice behaviorally classified as ¡°addicted¡± drinkers, suggesting that these genes may contribute to high and persistent ethanol consumption.