Melendez Roberto I, Rodd Zachary A, McBride William J, Murphy James M
Program in Psychobiology of Addictions, Department of Psychology, LD 124, Purdue School of Science, Indiana University-Purdue University at Indianapolis, IUPUI, 402 N. Blackford St., Indianapolis, IN 46202-3275, USA.
Drug Alcohol Depend. 2005 Mar 7;77(3):293-301. doi: 10.1016/j.drugalcdep.2004.08.024.
Sufficient evidence exists for the inclusion of the ventral pallidum (VP) into the category of a dopaminoceptive brain region. The effects of inhibiting dopamine D(1)- or D(2)-like receptors in the VP on (a) ethanol intake and (b) extracellular levels of dopamine, were investigated in the alcohol-preferring (P) rat. The D(1)-like antagonist, SCH-23390, and the D(2)-like antagonist, sulpiride (0.25-2 microg/0.5 microl) were bilaterally injected into the VP and ethanol (15%, v/v) intake was assessed in a 1 h limited access paradigm. The results indicate that microinjections of sulpiride significantly increased ethanol consumption (65% increase at the 2.0 microg dose). Whereas the D(1) antagonists SCH-23390 tended to decrease ethanol intake, the effect was not statistically significant. In a separate group of rats, reverse microdialysis of sulpiride and SCH-23390 (10-200 microM) were conducted in the VP of P rats. Local perfusion of only the 200 microM sulpiride dose significantly increased the extracellular levels of dopamine (maximal increase: 250% of baseline). On the other hand, local perfusion of SCH-23390 (10-200 microM) dose dependently increased the extracellular levels of dopamine 180-640% of baseline. Overall, the results of this study suggest that (a) tonic activation of D(2) postsynaptic receptors in VP imposes a limit on ethanol intake in the P rat; (b) there are few D(2) autoreceptors functioning in the VP; (c) there is tonic D(1)-like receptor mediated inhibitory feedback regulation of VP-dopamine release.
有充分证据表明腹侧苍白球（VP）属于多巴胺感受性脑区。本研究在嗜酒（P）大鼠中，探究了抑制VP中多巴胺D(1)或D(2)样受体对（a）乙醇摄入量和（b）细胞外多巴胺水平的影响。将D(1)样拮抗剂SCH-23390和D(2)样拮抗剂舒必利（0.25 - 2微克/0.5微升）双侧注射到VP中，并在1小时限时摄入模式下评估乙醇（15%，v/v）摄入量。结果表明，舒必利微量注射显著增加了乙醇消耗量（2.0微克剂量时增加65%）。而D(1)拮抗剂SCH-23390有降低乙醇摄入量的趋势，但该效应无统计学意义。在另一组大鼠中，对P大鼠的VP进行舒必利和SCH-23390（10 - 200微摩尔）的反向微透析。仅200微摩尔舒必利剂量的局部灌注显著增加了细胞外多巴胺水平（最大增加：基线的250%）。另一方面，SCH-23390（10 - 200微摩尔）的局部灌注使细胞外多巴胺水平剂量依赖性增加至基线的180 - 640%。总体而言，本研究结果表明：（a）VP中D(2)突触后受体的紧张性激活对P大鼠的乙醇摄入量有限制作用；（b）VP中几乎没有起作用的D(2)自身受体；（c）存在由D(1)样受体介导的VP - 多巴胺释放的紧张性抑制反馈调节。
