Department of Psychology and Neuroscience and Center for Neuroscience, University of Colorado Boulder, 2860 Wilderness Place, Boulder, CO, 80301, USA.
Psychopharmacology (Berl). 2019 Apr;236(4):1207-1218. doi: 10.1007/s00213-018-5126-y. Epub 2018 Nov 23.
Previous work has demonstrated that dopamine and adenosine receptors are involved in drug-seeking behaviors, yet the pharmacological interactions between these receptors in methamphetamine (MA) seeking are not well characterized. The present studies examined the role of the dopamine D-like receptors in MA seeking and identified the interactive effects of adenosine receptor stimulation.
Adult male Sprague-Dawley rats were trained to lever press for MA in daily 2-h self-administration sessions on a fixed-ratio 1 schedule for 10 consecutive days. After 1 day of abstinence, lever pressing was extinguished in six daily extinction sessions. Treatments were administered systemically prior to a 2-h reinstatement test session.
An increase in MA seeking was observed following the administration of the dopamine D-like agonist, quinpirole, or the D receptor agonist, 7-OH-DPAT. Stimulation of D or D receptors was ineffective at inducing MA seeking. Quinpirole-induced MA seeking was inhibited by D receptor antagonism (SB-77011A or PG01037), an adenosine A agonist, CPA, and an adenosine A agonist, CGS 21680. MA seeking induced by a MA priming injection or D receptor stimulation was inhibited by a pretreatment with the adenosine A agonist, CPA, but not the adenosine A agonist, CGS 21680.
These results demonstrate the sufficiency of dopamine D receptors to reinstate MA seeking that is inhibited when combined with adenosine A receptor stimulation.
先前的工作表明，多巴胺和腺苷受体参与了觅药行为，但在甲基苯丙胺（MA）觅药中，这些受体之间的药理学相互作用尚未得到很好的描述。本研究检查了多巴胺 D 样受体在 MA 觅药中的作用，并确定了腺苷受体刺激的相互作用效应。
成年雄性 Sprague-Dawley 大鼠接受训练，以在连续 10 天的每日 2 小时自我给药期间，通过固定比率 1 方案按压杠杆以获取 MA。在 1 天的禁欲后，在 6 个每日的消退课程中进行杠杆按压消退。在 2 小时的复吸测试课程之前，系统地给予治疗。
给予多巴胺 D 样激动剂喹吡罗或 D 受体激动剂 7-OH-DPAT 后，观察到 MA 觅药增加。刺激 D 或 D 受体不能诱导 MA 觅药。D 受体拮抗剂（SB-77011A 或 PG01037）、腺苷 A 激动剂 CPA 和腺苷 A 激动剂 CGS 21680 抑制了喹吡罗诱导的 MA 觅药。MA 引发的 MA 觅药或 D 受体刺激被腺苷 A 激动剂 CPA 的预处理抑制，但不是腺苷 A 激动剂 CGS 21680 的预处理。
这些结果表明，多巴胺 D 受体足以重新引发 MA 觅药，而当与腺苷 A 受体刺激结合时，这种觅药会受到抑制。
