Ethanol drinking reduces extracellular dopamine levels in the posterior ventral tegmental area of nondependent alcohol-preferring rats.

Ethanol drinking reduces extracellular dopamine levels in the posterior ventral tegmental area of nondependent alcohol-preferring rats.
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DOI:
10.1016/j.alcohol.2011.02.304
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发表时间:
2011-09
期刊:
Alcohol (Fayetteville, N.Y.)
影响因子:
--
通讯作者:
Morzorati SL
Morzorati SL
中科院分区:
其他
文献类型:
--
作者:
Engleman EA;Keen EJ;Tilford SS;Thielen RJ;Morzorati SL

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适度的乙醇暴露在非依赖性大鼠的中皮质边缘多巴胺系统中产生神经适应性变化,并增加体外和体内多巴胺神经元活动的测量。此外,适度饮酒和适度全身暴露可提高中皮质边缘投射区细胞外多巴胺水平。然而,在腹侧被盖区(VTA)中,适度饮酒对基础多巴胺水平的神经适应性变化尚未进行研究。在目前的研究中,成年雌性酒精偏好(P)大鼠被分为alcohol-naïve组、饮酒组和酒精剥夺组。饮酒组连续给予水和乙醇(15%,v/v) 8周。酒精剥夺组有6周的接触,然后是2周的酒精剥夺,2周的酒精再接触,然后是2周的酒精剥夺。被剥夺的大鼠对乙醇恢复表现出强烈的酒精剥夺效应。alcohol-naïve组只能持续获得水。在饮酒方案的最后一周,所有大鼠都被植入针对后VTA的单侧微透析探针,并进行无净通量微透析,以量化细胞外多巴胺水平和多巴胺清除率。结果显示,饮酒组后VTA基底细胞外多巴胺浓度显著低于未饮酒组和未饮酒组(分别为3.8±0.3 nM和5.0±0.5 nM [p < 0.02]和4.8±0.4 nM, [p < 0.05])。无酒精组和无酒精组之间的提取分数差异显著(p < 0.0002)(分别为72±2比46±4%),无酒精组和无酒精组之间差异不显著(p = 0.051)(无酒精组为61±6%)。数据表明,非依赖性P大鼠在中度慢性乙醇摄入后,后侧静脉血管内基础DA水平降低。这种减少部分可能是由于DA摄取增加,并且可能对维持乙醇饮用很重要。这些适应随着酒精剥夺而正常化,可能不会导致酒精剥夺效应。
Moderate ethanol exposure produces neuroadaptive changes in the mesocorticolimbic dopamine system in nondependent rats, and increases measures of dopamine neuronal activity in vitro and in vivo. Moreover, moderate ethanol drinking and moderate systemic exposure elevates extracellular dopamine levels in mesocorticolimbic projection regions. However, the neuroadaptive changes subsequent to moderate ethanol drinking on basal dopamine levels have not been investigated in the ventral tegmental area (VTA). In the current study, adult female alcohol-preferring (P) rats were divided into alcohol-naïve, alcohol drinking, and alcohol deprived groups. The alcohol drinking group had continuous access to water and ethanol (15%, v/v) for 8 weeks. The alcohol deprived group had 6 weeks of access followed by 2 weeks of ethanol deprivation, 2 weeks of ethanol re-exposure, followed again by 2 weeks of deprivation. The deprived rats demonstrated a robust alcohol deprivation effect upon ethanol reinstatement. The alcohol-naïve group had continuous access to water only. In the last week of the drinking protocol, all rats were implanted with unilateral microdialysis probes aimed at the posterior VTA and no-net-flux microdialysis was conducted to quantify extracellular dopamine levels and dopamine clearance. Results yielded significantly lower basal extracellular dopamine concentrations in the posterior VTA of the alcohol drinking group compared to the alcohol naive and alcohol deprived groups (3.8 ± 0.3 vs. 5.0 ± 0.5 [p < 0.02] and 4.8 ± 0.4 nM, [p < 0.05], respectively). Extraction fractions were significantly (p < 0.0002) different between the alcohol drinking and alcohol naive groups (72 ± 2 vs. 46 ± 4%, respectively) and not significantly different (p = 0.051) between alcohol deprived and alcohol naive groups (61 ± 6% for the alcohol deprived group). The data indicate that reductions in basal DA levels within the posterior VTA occur after moderate chronic ethanol intake in nondependent P rats. This reduction may result, in part, from increased DA uptake and may be important for the maintenance of ethanol drinking. These adaptations normalize with ethanol deprivation and may not contribute to the alcohol deprivation effect.
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