Effects of naltrexone on the ethanol-induced changes in the rat central dopaminergic system
Effects of naltrexone on the ethanol-induced changes in the rat central dopaminergic system
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DOI：
10.1093/alcalc/agh163
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发表时间：
2005-07-01
影响因子：
2.8
通讯作者：
Kim, YH
中科院分区：
文献类型：
--
作者：
Lee, YK;Park, SW;Kim, YH
阿片受体拮抗剂纳洛酮可能减少乙醇奖赏，但其神经化学机制尚不清楚。腹侧被盖区（VTA）向丘脑腹侧核的传入投射提供了一个潜在的底物，内源性阿片类物质可能通过该底物调节乙醇的多巴胺能奖赏效应。我们评估了酪氨酸羟化酶（TH）的mRNA水平，这是多巴胺合成中的一种主要调节酶，以及在慢性乙醇给药后伴或不伴纳曲酮的多巴胺及其代谢产物的水平。方法：将Sprague-Dawley大鼠暴露于慢性乙醇消耗（5%，4周），同时给予和不给予纳洛酮。用原位杂交和高效液相色谱法分别测定大鼠腹侧被盖区和黑质TH mRNA和纹状体多巴胺及其代谢产物的水平。结果：慢性乙醇消耗增加TH mRNA水平在VTA，但没有引起任何显着的变化在SN。用纳洛酮治疗，乙醇诱导的TH mRNA水平的增加在VTA中减少。慢性乙醇消耗并没有引起多巴胺及其代谢物在大多数大脑区域的水平的任何变化。仅在纹状体中，用纳洛酮治疗的乙醇消耗显著增加多巴胺水平。结论：这一发现支持存在的阿片和多巴胺能系统在腹侧被盖区介导的乙醇奖励的相互作用，因此纳洛酮减弱乙醇的奖励特性，通过干扰乙醇诱导的刺激中脑边缘多巴胺能通路。
Aims: The opioid antagonist naltrexone may reduce ethanol reward, but the underlying neurochemical mechanisms has yet to be clarified. The afferent projections to the nucleus accumbens from the ventral tegmental area (VTA) provide a potential substrate by which endogenous opioids may modulate the dopaminergic rewarding effects of ethanol. We assessed mRNA levels of tyrosine hydroxylase (TH), a major regulatory enzyme in the dopamine synthesis and levels of dopamine and its metabolites after chronic ethanol administration with and without concomitant naltrexone. Methods: Sprague-Dawley rats were exposed to chronic ethanol consumption (5%, 4 weeks) with and without concomitant naltrexone administration. Levels of TH mRNA in the VTA and substantia nigra (SN) and dopamine and its metabolites in the striatum of the rats were measured by in situ hybridization and by high performance liquid chromatography, respectively. Results: Chronic ethanol consumption increased TH mRNA levels in the VTA, but did not cause any significant change in the SN. With naltrexone treatment, ethanol-induced increase in the TH mRNA level was reduced in the VTA. Chronic ethanol consumption did not cause any change in the levels of dopamine and its metabolites in most brain regions. Only in the striatum, ethanol consumption with naltrexone treatment significantly increases the dopamine level. Conclusion: This finding supports the presence of interactions of opioid and dopaminergic systems in the VTA in mediating ethanol reward, and thus naltrexone attenuates the rewarding properties of ethanol by interfering with the ethanol-induced stimulation of the mesolimbic dopaminergic pathway.