Cabergoline decreases alcohol drinking and seeking behaviors via glial cell line-derived neurotrophic factor.
Cabergoline decreases alcohol drinking and seeking behaviors via glial cell line-derived neurotrophic factor.
复制标题
DOI：
10.1016/j.biopsych.2008.12.022
复制
发表时间：
2009-07-15
影响因子：
10.6
通讯作者：
Ron, Dorit
中科院分区：
文献类型：
--
作者：
Carnicella, Sebastien;Ahmadiantehrani, Somayeh;He, Dao-Yao;Nielsen, Carsten K.;Bartlett, Selena E.;Janak, Patricia H.;Ron, Dorit
卡麦角林是一种麦角胺衍生物，可在体外增加胶质细胞源性神经营养因子（GDNF）的表达。我们最近发现腹侧被盖区（VTA）的GDNF减少了饮酒的动机。因此，我们开始确定卡麦角林给药是否通过GDNF减少饮酒和寻求行为。采用逆转录聚合酶链反应（RT-PCR）和酶联免疫吸附试验（ELISA）检测GDNF水平。蛋白质印迹分析用于磷酸化实验。在大鼠中操作性自我给药和在小鼠中的两瓶选择程序被用来评估饮酒行为。在灭绝过程中测试的仪器性能被用来衡量酒精寻求行为。[35 S]GTPγS结合试验用于评估多巴胺D2受体（D2 R）的表达和功能。我们发现，在大鼠中，用卡麦角林处理多巴胺能样细胞系SH-SY 5 Y和全身给予卡麦角林导致GDNF水平增加和GDNF通路激活。卡麦角林治疗减少了饮酒和寻求酒精的行为，包括复发，其减少酒精消耗的作用局限于腹侧被盖区。最后，在GDNF杂合子敲除小鼠中，卡麦角林导致的GDNF表达增加和饮酒量减少被消除。总之，这些发现表明卡麦角林介导的GDNF通路上调可减少饮酒行为和复发。酒精滥用和成瘾是全世界毁灭性和代价高昂的问题。这项研究提出了卡麦角林可能是这些疾病的有效治疗的可能性。
Cabergoline is an ergotamine derivative that increases the expression of glial cell line-derived neurotrophic factor (GDNF) in vitro. We recently showed that GDNF in the ventral tegmental area (VTA) reduces the motivation to consume alcohol. We therefore set out to determine whether cabergoline administration decreases alcohol-drinking and -seeking behaviors via GDNF. Reverse transcription polymerase chain reaction (RT-PCR) and Enzyme-Linked ImmunoSorbent Assay (ELISA) were used to measure GDNF levels. Western blot analysis was used for phosphorylation experiments. Operant self-administration in rats and a two-bottle choice procedure in mice were used to assess alcohol-drinking behaviors. Instrumental performance tested during extinction was used to measure alcohol-seeking behavior. The [35S]GTPγS binding assay was used to assess the expression and function of the dopamine D2 receptor (D2R). We found that treatment of the dopaminergic-like cell line SH-SY5Y with cabergoline and systemic administration of cabergoline in rats resulted in an increase in GDNF level and in the activation of the GDNF pathway. Cabergoline treatment decreased alcohol-drinking and -seeking behaviors including relapse, and its action to reduce alcohol consumption was localized to the VTA. Finally, the increase in GDNF expression and the decrease in alcohol consumption by cabergoline were abolished in GDNF heterozygous knockout mice. Together, these findings suggest that cabergoline-mediated upregulation of the GDNF pathway attenuates alcohol-drinking behaviors and relapse. Alcohol abuse and addiction are devastating and costly problems worldwide. This study puts forward the possibility that cabergoline might be an effective treatment for these disorders.
登录
查看更多内容
影响因子：
3.4
作者：
Escher, Tobie;Mittleman, Guy
通讯作者：
Mittleman, Guy
影响因子：
5.3
作者：
Jeanblanc, J;He, DY;Ron, D
通讯作者：
Ron, D
影响因子：
3.4
作者：
Airavaara, M;Planken, A;Ahtee, L
通讯作者：
Ahtee, L
影响因子：
2.3
作者：
Camicella, Sebastien;Amamoto, Ryoji;Ron, Dorit
通讯作者：
Ron, Dorit
影响因子：
5.8
作者：
Colao, Annamaria;Galderisi, Maurizio;Lombardi, Gaetano
通讯作者：
Lombardi, Gaetano