The peripheral dopamine 2 receptor antagonist domperidone attenuates ethanol enhancement of dopamine levels in the nucleus accumbens.
The peripheral dopamine 2 receptor antagonist domperidone attenuates ethanol enhancement of dopamine levels in the nucleus accumbens.
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DOI：
10.1111/acer.14775
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发表时间：
2022-03
期刊：
影响因子：
--
通讯作者：
Steffensen SC
中科院分区：
文献类型：
--
作者：
Obray JD;Jang EY;Klomp AM;Small CA;Richardson AP;LeBaron JJ;Lee JG;Yorgason JT;Yang CH;Steffensen SC
腹侧被盖区（VTA）的多巴胺神经元放电和中脑核的多巴胺释放与奖赏学习有关。已知乙醇会增加腹侧被盖区的多巴胺神经元放电和延髓核的多巴胺水平。尽管如此，增强体内和体外击发所需的乙醇剂量之间存在一些差异。在本研究中，我们研究了外周多巴胺2亚型受体拮抗剂对乙醇对多巴胺神经传递的影响。在四种不同剂量的EtOH中给予乙醇后评估血浆儿茶酚胺水平。微透析和伏安法被用来评估多潘立酮预处理对乙醇介导的多巴胺释放增加的影响。位置条件反射范式被用来评估乙醇的条件偏好和多潘立酮预处理是否改变了这种偏好。采用旷场和翻正反射消失实验观察多潘立酮对乙醇诱导的镇静作用。采用旋转棒装置评价多潘立酮对乙醇所致运动障碍的影响。在非生理条件下，在中等剂量（1.0和2.0 g/kg）乙醇下，多潘立酮减弱了乙醇对中脑边缘多巴胺释放的增强作用。多潘立酮在2.0 g/kg时也可降低EtOH诱导的镇静作用。多潘立酮不改变乙醇条件性位置偏爱，也不影响乙醇诱导的运动障碍。这些结果表明，外周多巴胺2受体介导的乙醇对非生理多巴胺神经传递的影响，虽然这些影响是不相关的奖励性质的乙醇。
Dopamine neuron firing in the ventral tegmental area (VTA) and dopamine release in the nucleus accumbens have been implicated in reward learning. Ethanol is known to increase both dopamine neuron firing in the VTA and dopamine levels in the nucleus accumbens. Despite this, some discrepancies exist between the dose of ethanol required to enhance firing in vivo and ex vivo. In the present study we investigated the effects of peripheral dopamine 2 subtype receptor antagonism on ethanol’s effects on dopamine neurotransmission. Plasma catecholamine levels were assessed following ethanol administration across four different doses of EtOH. Microdialysis and voltammetry were used to assess the effects of domperidone pretreatment on ethanol-mediated increases in dopamine release in the nucleus accumbens. A place conditioning paradigm was used to assess conditioned preference for ethanol and whether domperidone pretreatment altered this preference. Open-field and loss-of-righting reflex paradigms were used to assess the effects of domperidone on ethanol-induced sedation. A rotarod apparatus was used to assess the effects of domperidone on ethanol-induced motor impairment. Domperidone attenuated ethanol’s enhancement of mesolimbic dopamine release under non-physiological conditions at intermediate (1.0 and 2.0 g/kg) doses of ethanol. Domperidone also decreased EtOH-induced sedation at 2.0 g/kg. Domperidone did not alter ethanol conditioned place preference nor did it affect ethanol-induced motor impairment. These results show that peripheral dopamine 2 receptors mediate some of the effects of ethanol on nonphysiological dopamine neurotransmission, although these effects are not related to the rewarding properties of ethanol.
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影响因子：
7.3
作者：
Feduccia, A. A.;Simms, J. A.;Bartlett, S. E.
通讯作者：
Bartlett, S. E.
影响因子：
5
作者：
Jang, Eun Young;Choe, Eun Sang;Yang, Chae Ha
通讯作者：
Yang, Chae Ha
DOI：
10.1097/00000374-199911000-00019
发表时间：
1999-11-01
影响因子：
3.2
作者：
Brodie, MS;Pesold, C;Appel, SB
通讯作者：
Appel, SB
乙醇对自由移动大鼠的腹侧换段区域神经元产生多种电生理作用。
影响因子：
3.4
作者：
Doyon WM;Ostroumov A;Ontiveros T;Gonzales RA;Dani JA
通讯作者：
Dani JA
影响因子：
2.3
作者：
Sullivan, Jenna M.;Risacher, Shannon L.;Normandin, Marc D.;Yoder, Karmen K.;Froehlich, Janice C.;Morris, Evan D.
通讯作者：
Morris, Evan D.