Department of Anesthesiology, Perioperative and Pain Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, No.109, Xue-yuan Road(West), Lu-cheng District, Wenzhou, 325027, China.
Department of Anesthesiology, Suzhou Municipal Hospital, Suzhou, 234000, China.
Neurochem Res. 2018 Dec;43(12):2393-2403. doi: 10.1007/s11064-018-2667-8. Epub 2018 Oct 24.
Propofol has been proven to be potentially abused by humans and laboratory animals; however, studies that have examined propofol relapse behavior are limited, and its underlying mechanism remains unclear. In this study, we examined whether basolateral amygdala-specific or systematic administration of the dopamine receptor antagonist alters cue-induced propofol-seeking behaviors in a rat model. Male Sprague-Dawley rats first received 14 days of propofol self-administration training, where active nose poke resulted in the delivery of propofol infusion paired with a tone and light cues. After 1-30 days of forced abstinence, the cue-induced propofol-seeking behaviors were tested in the operant chamber. We demonstrated, for the first time, after a few days of withdrawal from intravenous bolus administration of propofol, propofol-related cues could induce robust reinstatement of drug-seeking behavior. Systematic administration of dopamine D receptor antagonist (SCH-23390) or dopamine D receptor antagonist (spiperone) inhibited propofol relapse behavior induced by drug-related cues. Furthermore, we show that microinfusion of SCH-23390 into basolateral amygdala dose-dependently attenuated cue-induced propofol drug-seeking behavior, whereas infusion of spiperone had no effect on the propofol relapse behavior. Our results reveal the involvement of dopamine receptors within the basolateral amygdala in the cue-induced propofol relapse behavior in rats.
丙泊酚已被证明易被人类和实验动物滥用；然而，检查丙泊酚复吸行为的研究有限，其潜在机制仍不清楚。在这项研究中，我们研究了是否基底外侧杏仁核特异性或系统性给予多巴胺受体拮抗剂会改变大鼠模型中线索诱导的丙泊酚觅药行为。雄性 Sprague-Dawley 大鼠首先接受 14 天的丙泊酚自我给药训练，主动鼻探测导致丙泊酚输注与声音和灯光线索配对。在强制禁欲 1-30 天后，在操作室中测试线索诱导的丙泊酚觅药行为。我们首次证明，在停止静脉推注丙泊酚几天后，丙泊酚相关线索可诱导强烈的觅药行为复吸。系统给予多巴胺 D 受体拮抗剂（SCH-23390）或多巴胺 D 受体拮抗剂（spiperone）可抑制药物相关线索诱导的丙泊酚复吸行为。此外，我们表明，将 SCH-23390 微量注入基底外侧杏仁核可剂量依赖性地减弱线索诱导的丙泊酚觅药行为，而 spiperone 对丙泊酚复吸行为没有影响。我们的研究结果表明，基底外侧杏仁核内的多巴胺受体参与了大鼠线索诱导的丙泊酚复吸行为。
