Thielen R J, Engleman E A, Rodd Z A, Murphy J M, Lumeng L, Li T-K, McBride W J
Department of Psychiatry, Institute of Psychiatric Research, Indiana University Medical Center, 791 Union Drive, Indianapolis, IN 46202-4887, USA.
J Pharmacol Exp Ther. 2004 Apr;309(1):216-25. doi: 10.1124/jpet.103.059790. Epub 2004 Jan 12.
The alcohol deprivation effect is a temporary increase in the intake of, or preference for, ethanol after a period of deprivation that may result from persistent changes in key limbic regions thought to regulate alcohol drinking, such as the nucleus accumbens. The present study tested the hypothesis that chronic alcohol drinking under continuous 24-h free-choice conditions alters dopamine and serotonin neurotransmission in the nucleus accumbens and that these alterations persist in the absence of alcohol. Using the no-net-flux microdialysis method, the steady-state extracellular concentration (point of no-net-flux) for dopamine was approximately 25% higher in the adult female alcohol-preferring P rats given prior access to 10% ethanol, even after 2 weeks of ethanol abstinence, compared with the P rats gives access only to water. However, the extracellular concentration of serotonin was approximately 35% lower in animals given 8 weeks of continuous access to ethanol compared with water controls and animals deprived of ethanol for 2 weeks. The effect of local perfusion with 100 microM sulpiride (D(2) receptor antagonist) and 35 microM 1-(m-chlorophenyl)-biguanide (5-hydroxytryptamine(3) receptor agonist) on dopamine overflow were reduced approximately 33% in both groups of ethanol-exposed P rats compared with water controls. Free-choice alcohol drinking by P rats alters dopamine and serotonin neurotransmission in the nucleus accumbens, and many of these effects persist for at least 2 weeks in the absence of ethanol, suggesting that these underlying persistent changes may be in part responsible for increased ethanol drinking observed in the alcohol-deprivation effect.
酒精剥夺效应是指在一段时间的剥夺后，乙醇摄入量或对乙醇的偏好会暂时增加，这可能是由于被认为调节饮酒行为的关键边缘区域（如伏隔核）发生了持续变化所致。本研究检验了以下假设：在连续24小时自由选择的条件下长期饮酒会改变伏隔核中的多巴胺和5-羟色胺神经传递，并且这些改变在无酒精的情况下会持续存在。使用无净通量微透析方法，与只给予水的P大鼠相比，成年雌性嗜酒P大鼠在事先接触10%乙醇后，即使在戒酒2周后，多巴胺的稳态细胞外浓度（无净通量点）仍高出约25%。然而，与水对照组和被剥夺乙醇2周的动物相比，连续8周接触乙醇的动物的5-羟色胺细胞外浓度大约低35%。与水对照组相比，两组接触乙醇的P大鼠中，用100微摩尔/升舒必利（D₂受体拮抗剂）和35微摩尔/升1-（间氯苯基）-双胍（5-羟色胺₃受体激动剂）进行局部灌注对多巴胺溢出的影响降低了约33%。P大鼠自由选择饮酒会改变伏隔核中的多巴胺和5-羟色胺神经传递，并且其中许多影响在无乙醇的情况下至少持续2周，这表明这些潜在的持续变化可能部分导致了在酒精剥夺效应中观察到的乙醇摄入量增加。
