Department of Anesthesiology of the 2nd Affiliated Hospital and Institute of Neuroendocrinology, Wenzhou Medical College, Wenzhou, Zhejiang 325000, PR China.
Neuroscience. 2013 Feb 12;231:373-83. doi: 10.1016/j.neuroscience.2012.11.002. Epub 2012 Nov 29.
As a widely used intravenous short-acting anesthetic, propofol is recently indicated by clinical and animal studies for its abuse potential, but the mechanism underlying propofol abuse is largely unknown. This study examined the contribution of dopamine receptor subtype (D1 and D2 receptors) and neuroanatomical locus (i.e. nuclear accumbens) in the maintenance of propofol self-administration in rats. After the acquisition and maintenance of self-administration of propofol (1.7 mg/kg/infusion) under a fixed ratio (FR1) schedule of reinforcement over 14 days, rats were treated by either intraperitoneal injection or intra-nucleus accumbens (NAc) injection of D1 receptor antagonist (SCH23390) or D2 receptor antagonists (spiperone and eticlopride) 10 min prior to the subsequent propofol self-administration. We demonstrated (i) systemic administration of SCH23390 (10, 30, 100 μg/kg, i.p.) dose-dependently decreased the rate of propofol-maintained self-administration, suggesting a critical role of the D1 receptor in mediating propofol self-administration; (ii) the blockade of the propofol self-administration by SCH23390 was specific since spiperone and eticlopride did not affect propofol self-administration and SCH23390 at these doses did not affect food-maintained responding under an FR5 schedule; (iii) intra-accumbenal injection of SCH23390 (2.5 μg/site) but not eticopride (3.0 μg/site) attenuated the propofol self-administration, localizing nuclear accumbal D1 receptors as a critical locus in the reinforcement of propofol. Together, these findings provide the first direct evidence that D1 receptors in nuclear accumbens play an important role in the maintenance of propofol self-administration.
作为一种广泛使用的静脉内短效麻醉剂，丙泊酚最近在临床和动物研究中被指出具有滥用潜力，但丙泊酚滥用的机制在很大程度上尚不清楚。本研究考察了多巴胺受体亚型（D1 和 D2 受体）和神经解剖学位置（即伏隔核）在维持大鼠丙泊酚自我给药中的作用。在通过固定比率（FR1）强化方案获得和维持丙泊酚（1.7mg/kg/输注）自我给药 14 天后，在随后的丙泊酚自我给药之前 10 分钟，通过腹腔内注射或核内伏隔核（NAc）注射 D1 受体拮抗剂（SCH23390）或 D2 受体拮抗剂（spiperone 和 eticlopride）对大鼠进行治疗。我们证明了（i）SCH23390（10、30、100μg/kg，ip）的全身给药剂量依赖性地降低了丙泊酚维持的自我给药率，表明 D1 受体在介导丙泊酚自我给药中起关键作用；（ii）SCH23390 阻断丙泊酚自我给药是特异性的，因为 spiperone 和 eticlopride 不影响丙泊酚自我给药，并且在这些剂量下，SCH23390 不影响 FR5 方案下的食物维持反应；（iii）NAc 内注射 SCH23390（2.5μg/部位）而不是 eticopride（3.0μg/部位）减弱了丙泊酚的自我给药，将核内伏隔核 D1 受体定位为强化丙泊酚的关键部位。总之，这些发现提供了直接证据，表明核内伏隔核中的 D1 受体在维持丙泊酚自我给药中起着重要作用。
