Sari Youssef, Bell Richard L, Zhou Feng C
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Alcohol Clin Exp Res. 2006 Jan;30(1):46-56. doi: 10.1111/j.1530-0277.2006.00010.x.
Dopaminergic (DA) activity in the extended amygdala (EA) has been known to play a pivotal role in mediating drug and alcohol addiction. Alterations of DA activity within the EA after chronic exposure to alcohol or substances of abuse are considered a major mechanism for the development of alcoholism and addiction. To date, it is not clear how different patterns of chronic alcohol drinking affect DA receptor levels. Therefore, the current studies investigated the effects of chronic ethanol consumption, with or without deprivations, on D1 and D2 receptor densities within the EA.
Inbred alcohol-preferring (iP) rats were divided into 3 groups with the following treatments: (1) water for 14 weeks; (2) continuous alcohol (C-Alc) for 14 weeks [24-hour concurrent access to 15 and 30% (v/v) ethanol]; or (3) repeatedly deprived of alcohol (RD-Alc) (24-hour concurrent access to 15 and 30% ethanol for 6 weeks, followed by 2 cycles of 2 weeks of deprivation of and 2 weeks of reexposure to ethanol access). At the end of 14 weeks, the rats were killed for autoradiographic labeling of D1 and D2 receptors.
Compared with the water control group, both the C-Alc and the RD-Alc groups displayed increases in D1 receptor binding density in the anterior region of the Acb core, whereas the RD-Alc group displayed additional increases in D1 receptor binding density in anterior regions of the lateral and intercalated nuclei of the amygdala. Additionally, both C-Alc and RD-Alc rats displayed increases in D2 receptor binding density in anterior regions of the Acb shell and core, whereas RD-Alc rats displayed additional increases in D2 receptor binding density in the dorsal striatum.
The results of this study indicate that 14-week extended alcohol drinking with continuous chronic or repeated deprivations increase binding sites of D1 and D2 receptors in specific regions of the EA with greater sensitivity in the anterior regions. The repeated deprivation has greater effect on altering D1 and D2 receptor binding sites in the Acb, dorsal striatum, and subamygdala regions. The current result indicates that the two drinking paradigms may have common as well as differential mechanisms on alteration of dopamine receptor-binding sites in specific regions of the EA.
已知终纹床核（extended amygdala，EA）中的多巴胺能（DA）活性在介导药物和酒精成瘾中起关键作用。长期接触酒精或滥用物质后，EA内DA活性的改变被认为是酗酒和成瘾发展的主要机制。迄今为止，尚不清楚不同模式的长期饮酒如何影响DA受体水平。因此，当前研究调查了长期乙醇摄入（有无剥夺期）对EA内D1和D2受体密度的影响。
将近交系嗜酒（iP）大鼠分为3组，进行如下处理：（1）饮用14周水；（2）连续饮用酒精（C-Alc）14周[同时24小时可获取15%和30%（v/v）乙醇]；或（3）反复戒酒（RD-Alc）（24小时同时可获取15%和30%乙醇6周，随后进行2个周期，每个周期为2周戒酒和2周重新接触乙醇）。在14周结束时，处死大鼠以进行D1和D2受体的放射自显影标记。
与水对照组相比，C-Alc组和RD-Alc组在伏隔核核心前部区域的D1受体结合密度均增加，而RD-Alc组在杏仁核外侧核和闰核前部区域的D1受体结合密度有额外增加。此外，C-Alc组和RD-Alc组大鼠在伏隔核壳和核心前部区域的D2受体结合密度均增加，而RD-Alc组大鼠在背侧纹状体的D2受体结合密度有额外增加。
本研究结果表明，持续慢性或反复剥夺的14周延长饮酒会增加EA特定区域中D1和D2受体的结合位点，在前部区域更为敏感。反复剥夺对改变伏隔核、背侧纹状体和杏仁核下区域的D1和D2受体结合位点有更大影响。当前结果表明，这两种饮酒模式在EA特定区域多巴胺受体结合位点改变方面可能有共同和不同的机制。
