D1 dopamine receptor regulates alcohol-motivated behaviors in the bed nucleus of the stria terminalis in alcohol-preferring (P) rats
D1 dopamine receptor regulates alcohol-motivated behaviors in the bed nucleus of the stria terminalis in alcohol-preferring (P) rats
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DOI：
10.1002/syn.10181
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发表时间：
2003-04-01
期刊：
影响因子：
2.3
通讯作者：
June, HL
中科院分区：
文献类型：
--
作者：
Eiler, WJA;Seyoum, R;June, HL
最近的研究表明，终纹床核（BST）是介导药物相关行为的潜在脑底物。神经解剖学研究表明，从BST到腹侧被盖区（VTA）存在相互投射，这是一种多巴胺奖励底物，被认为在酒精滥用中起作用。在本研究中，我们评估了BST的D-1和D-2多巴胺受体在调节酒精和蔗糖驱动行为中的作用。酒精偏好(P)大鼠在FR4操作计划下接受训练，自我管理EtOH （10% v/v）或蔗糖（2% w/v）。训练后，我们评估了竞争性D-1 （SCH 23390; 0.5-20.0马克杯）和D-2 （eticlopri,de; 0.5-20.0马克杯）多巴胺拮抗剂选择性降低etoh维持反应的能力。非选择性阿片类拮抗剂纳曲酮（5-30.0马克杯）作为对照剂。结果表明，SCH 23390剂量依赖性地降低了酒精刺激反应。20.0杯的剂量降低了反应，约为对照水平的97%。SCH 23390也降低了蔗糖的反应；然而，最高剂量（2.5、20.0马克杯）的影响程度明显较低（为对照水平的68-79%）。相比之下，依替氯pride仅在10.0马克杯剂量下不能显著改变酒精反应和减少蔗糖反应。与多巴胺拮抗剂不同，所有纳曲酮剂量都不能改变EtOH或蔗糖维持反应。结果表明，D-1受体，而D-2受体和阿片受体，在选择性调节etoh驱动的BST行为中起着重要作用。
Recent studies have implicated the bed nucleus of the stria terminalis (BST) as a potential brain substrate for mediating drug-related behaviors. Neuroanatomical studies have demonstrated that reciprocal projections exist from the BST to the ventral tegmental area (VTA), a dopamine reward substrate proposed to play a role in alcohol abuse. In the present study, we evaluated the role of the D-1 and D-2 dopamine receptors of the BST in regulating alcohol and sucrose-motivated behaviors. Alcohol-preferring (P) rats were trained under an FR4 operant schedule to self-administer either EtOH (10% v/v) or sucrose (2% w/v). Following training, we evaluated the capacity of a competitive D-1 (SCH 23390; 0.5-20.0 mug) and a D-2 (eticlopri,de; 0.5-20.0 mug) dopamine antagonist to selectively reduce EtOH-maintained responding. Naltrexone, (5-30.0 mug), the nonselective opioid antagonist, was used as a reference agent. The results showed that SCH 23390 dose-dependently reduced alcohol-motivated responding. Responding was reduced with the 20.0 mug dose to about 97% of control levels. SCH 23390 also reduced sucrose responding; however, the magnitude of effects was substantially lower with the highest doses (2.5, 20.0 mug) (68-79% of control levels). In contrast, eticlopride failed to significantly alter alcohol responding and reduced sucrose responding only with the 10.0 mug dose. Unlike the dopamine-antagonists, all naltrexone doses failed to alter EtOH or sucrose-maintained responding. The results suggest a salient role for the D-1, but not the D-2 and opioid receptors in selectively modulating EtOH-motivated behaviors in the BST.