Hauser S R, Deehan G A, Dhaher R, Knight C P, Wilden J A, McBride W J, Rodd Z A
Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, United States.
Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, United States.
Neuroscience. 2015 Jun 4;295:243-51. doi: 10.1016/j.neuroscience.2015.03.030. Epub 2015 Mar 24.
Clinical and preclinical research suggest that activation of the mesolimbic dopamine (DA) system is involved in mediating the rewarding actions of drugs of abuse, as well as promoting drug-seeking behavior. Inhibition of DA D1 receptors in the nucleus accumbens (Acb) can reduce ethanol (EtOH)-seeking behavior of non-selective rats triggered by environmental context. However, to date, there has been no research on the effects of D1 receptor agents on EtOH- seeking behavior of high alcohol-preferring (P) rats following prolonged abstinence. The objective of the present study was to examine the effects of microinjecting the D1 antagonist SCH 23390 or the D1 agonist A-77636 into the Acb shell or Acb core on spontaneous recovery of EtOH-seeking behavior. After 10 weeks of concurrent access to EtOH and water, P rats underwent seven extinction sessions (EtOH and water withheld), followed by 2 weeks in their home cages without access to EtOH or operant sessions. In the 2nd week of the home cage phase, rats were bilaterally implanted with guide cannula aimed at the Acb shell or Acb core; rats were allowed 7d ays to recover before EtOH-seeking was assessed by the Pavlovian Spontaneous Recovery (PSR) model. Administration of SCH23390 (1μg/side) into the Acb shell inhibited responding on the EtOH lever, whereas administration of A-77636 (0.125μg/side) increased responding on the EtOH lever. Microinfusion of D1 receptor agents into the Acb core did not alter responding on the EtOH lever. Responses on the water lever were not altered by any of the treatments. The results suggest that activation of D1 receptors within the Acb shell, but not Acb core, are involved in mediating PSR of EtOH-seeking behavior of P rats.
临床和临床前研究表明，中脑边缘多巴胺（DA）系统的激活参与介导滥用药物的奖赏作用以及促进觅药行为。伏隔核（Acb）中DA D1受体的抑制可减少由环境背景触发的非选择性大鼠的乙醇（EtOH）觅求行为。然而，迄今为止，尚无关于D1受体药物对长期禁欲后高乙醇偏好（P）大鼠的EtOH觅求行为影响的研究。本研究的目的是检查向Acb壳或Acb核微量注射D1拮抗剂SCH 23390或D1激动剂A - 77636对EtOH觅求行为自发恢复的影响。在同时接触EtOH和水10周后，P大鼠接受7次消退训练（停止供应EtOH和水），然后在其笼舍中饲养2周，期间不接触EtOH或进行操作性训练。在笼舍饲养阶段的第2周，大鼠双侧植入针对Acb壳或Acb核的引导套管；在通过巴甫洛夫自发恢复（PSR）模型评估EtOH觅求行为之前，让大鼠恢复7天。向Acb壳注射SCH23390（1μg/侧）可抑制对EtOH杠杆的反应，而注射A - 77636（0.125μg/侧）则增加对EtOH杠杆的反应。向Acb核微量注射D1受体药物未改变对EtOH杠杆的反应。任何处理均未改变对水杠杆的反应。结果表明，Acb壳而非Acb核内的D1受体激活参与介导P大鼠EtOH觅求行为的PSR。
