Salsolinol produces reinforcing effects in the nucleus accumbens shell of alcohol-preferring (P) rats.
Salsolinol produces reinforcing effects in the nucleus accumbens shell of alcohol-preferring (P) rats.
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Salsolinol 对嗜酒 (P) 大鼠的伏隔核壳产生增强作用。
DOI：
10.1097/01.alc.0000056612.89957.b4
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Li,Ting-Kai
中科院分区：
文献类型：
--
作者：
Rodd,ZacharyA;Bell,RichardL;Zhang,Ying;Goldstein,Avram;Zaffaroni,Alejandro;McBride,WilliamJ;Li,Ting-Kai
背景：沙龙醇(Salsolinol，SAL)的形成被认为是导致酒精中毒和酗酒的一个因素。如果SAL是在长期饮酒条件下形成的，那么它可能会通过自我奖励而导致酒精成瘾。由于乙醛与多巴胺的非酶缩合可形成SAL，因此在伏隔核壳中检测SAL的增强作用，该部位被认为是参与调节饮酒行为的多巴胺丰富部位。成年雌性酒精嗜好(P)大鼠立体定向植入指向伏隔核壳的引导管。术后7~10d，将大鼠固定在电解微量输液换能器上，置于两级实验室中，接受100nL改良人工脑脊液或0.03、0.3、3.0或12.5fmoL/100nL的改良人工脑脊液(μM Sal)。治疗持续时间为4小时，每48小时进行一次黑暗周期。在一项单独的实验中测试了联合输注10~400μM舒必利(在4次采集后的第5次和第6次)对3.0μM SAL的颅内自主给药的影响。结果：给予0.3~12.5μM SAL的P大鼠每一次的输液次数明显多于单独使用ACSF3μM SAL的大鼠(例如，ACSF3μM SAL的输注次数为50次，而ACSF组的输注次数为10次或更少)，并且对活动水平的反应明显高于非活动水平水平。与舒必利共输注100或400μM舒必利可将主动杠杆的反应(80-100次/次)降低到非主动杠杆的水平(每次舒必利少于10次)。这种作用是可逆的，因为在第7阶段单独给予SAL可以恢复对主动杠杆的反应。结论：SAL在P大鼠伏隔核壳层以药理学上可能的浓度增强，这种增强作用部分是通过D2/D3样受体介导的。
Background:The formation of salsolinol (SAL) has been hypothesized to be a factor contributing to alcoholism and alcohol abuse. If SAL is formed under chronic alcohol‐drinking conditions, then it may contribute to alcohol addiction by being rewarding itself. Because SAL can be formed by the nonenzymatic condensation of acetaldehyde with dopamine, the reinforcing effects of SAL were tested in the nucleus accumbens shell, a dopamine‐rich site considered to be involved in regulating alcohol‐drinking behavior.Methods:The intracranial self‐administration technique was used to test the reinforcing properties of SAL. Adult, female alcohol‐preferring (P) rats were stereotaxically implanted with guide cannulae aimed at the nucleus accumbens shell. After 7 to 10 days to allow recovery from surgery, P rats were attached to the electrolytic microinfusion transducer system, placed in two‐lever experimental chambers, and allowed to respond for the self‐infusion of 100 nl of modified artificial cerebrospinal fluid (aCSF) or 0.03, 0.3, 3.0, or 12.5 μM SAL (3–1250 fmol/100 nl). Sessions were 4 hr in duration and were conducted in the dark cycle every 48 hr. The effects of coinfusing 10 to 400 μM sulpiride (given in sessions 5 and 6 after four acquisition sessions) on the intracranial self‐administration of 3.0 μM SAL were tested in a separate experiment.Results:P rats given 0.3 to 12.5 μM SAL received significantly more infusions per session than did the group given aCSF alone (e.g., 50 infusions for 3.0 μM SAL versus 10 or fewer infusions for the aCSF group) and responded significantly more on the active than inactive lever. Coinfusion of 100 or 400 μM sulpiride reduced the responding on the active lever (80–100 responses/session without sulpiride) to levels observed for the inactive lever (fewer than 10 responses/session with sulpiride). This effect was reversible because giving SAL alone in session 7 reinstated responding on the active lever.Conclusions:SAL is reinforcing in the nucleus accumbens shell of P rats at concentrations that are pharmacologically possible, and these reinforcing actions are mediated in part by D2/D3‐like receptors.
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影响因子：
56.9
作者：
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DOI：
10.1124/jpet.300.3.882
发表时间：
2002-03-01
影响因子：
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作者：
Liu, X;Weiss, F
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作者：
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