Duarte Christine, Lefebvre Cécil, Chaperon Frédérique, Hamon Michel, Thiébot Marie-Hélène
INSERM U.288, Faculty of Medicine Pitié-Salpêtrière, Paris, France.
Neuropsychopharmacology. 2003 Nov;28(11):1903-15. doi: 10.1038/sj.npp.1300276.
The present study addressed the role of dopaminergic D(3) receptors (D(3)R) in motivational processes in rats. The effects of the selective D(3)R partial agonist, BP 897 (0.25-1 mg/kg, i.p.), on the establishment and the expression of conditioned place preference (CPP) supported by food, morphine (4 mg/kg, s.c.), or cocaine (2 mg/kg, s.c.) were investigated using an unbiased, one-compartment, place-conditioning procedure. When administered alone, BP 897 (0.05-2 mg/kg, i.p.) did not support CPP; on the contrary, conditioned place avoidance (CPA) was observed at 1 mg/kg, suggesting that this dose of BP 897 could be perceived as aversive. When given before each cocaine injection during the conditioning phase, BP 897 (1 mg/kg) prevented the establishment of CPP, and a single administration of BP 897 (0.5 and 1 mg/kg) before the test session impaired the expression of cocaine CPP. In contrast, neither the establishment nor the expression of food- and morphine-CPP were significantly altered by BP 897 (up to 1 mg/kg), whereas the full but less selective D(3)/D(2)R agonists, 7-OH-DPAT (0.5-2 mug/kg, s.c.) and quinelorane (1 mug/kg, s.c.), prevented the acquisition of food CPP. In a within-session extinction schedule of lever pressing for food, BP 897 (0.06-2 mg/kg) was ineffective in potentiating response reinstatement induced by the noncontingent delivery of two food pellets, in contrast with quinelorane and 7-OH-DPAT where previous studies showed to be efficient in this respect (Duarte et al, 2003). These results indicate that BP 897 has no positive appetitive value on its own, and that a moderate degree of stimulation of D(3)R is not sufficient to modulate food-primed food-seeking behavior or alter incentive motivation for food, morphine, and/or their associated cues. However, D(3)R are likely involved in the perception of the rewarding value of cocaine and cocaine-paired cues. This suggests that the appetitive effects of cocaine are subserved by mechanisms different, at least in part, from those of morphine and food, and that D(3)R play a role only in the former.
本研究探讨了多巴胺能D(3)受体（D(3)R）在大鼠动机过程中的作用。使用无偏倚的单室位置条件化程序，研究了选择性D(3)R部分激动剂BP 897（0.25 - 1毫克/千克，腹腔注射）对由食物、吗啡（4毫克/千克，皮下注射）或可卡因（2毫克/千克，皮下注射）支持的条件性位置偏好（CPP）的建立和表达的影响。单独给药时，BP 897（0.05 - 2毫克/千克，腹腔注射）不支持CPP；相反，在1毫克/千克时观察到条件性位置回避（CPA），表明该剂量的BP 897可被视为厌恶的。在条件化阶段，在每次可卡因注射前给予BP 897（1毫克/千克）可阻止CPP的建立，并且在测试前单次给予BP 897（0.5和1毫克/千克）会损害可卡因CPP的表达。相比之下，BP 897（高达1毫克/千克）对食物和吗啡CPP的建立和表达均无显著影响，而完全但选择性较低的D(3)/D(2)R激动剂7 - OH - DPAT（0.5 - 2微克/千克，皮下注射）和喹吡罗（1微克/千克，皮下注射）可阻止食物CPP的获得。在按食物进行的杠杆按压的会话内消退程序中，BP 897（0.06 - 2毫克/千克）在增强由非偶然性给予两个食物颗粒诱导的反应恢复方面无效，这与喹吡罗和7 - OH - DPAT相反，先前的研究表明它们在这方面是有效的（Duarte等人，2003年）。这些结果表明，BP 897本身没有正向的食欲价值，并且对D(3)R的适度刺激不足以调节食物引发的觅食行为或改变对食物、吗啡和/或其相关线索的激励动机。然而，D(3)R可能参与了对可卡因和可卡因配对线索的奖励价值的感知。这表明，可卡因的食欲效应至少部分地由与吗啡和食物不同的机制介导，并且D(3)R仅在前一种情况中起作用。
