Rodríguez De Fonseca F, Rubio P, Martín-Calderón J L, Caine S B, Koob G F, Navarro M
Departamento de Psicobiología, Facultad de Psicología, Universidad Complutense, Madrid, Spain.
Eur J Pharmacol. 1995 Feb 14;274(1-3):47-55. doi: 10.1016/0014-2999(94)00708-f.
The present study investigated the effects of systemic administration of the putative dopamine D3 receptor agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) on the acquisition and expression of morphine-induced place preference in male Wistar rats. Using a a 3-day schedule of conditioning it was found that 7-OH-DPAT in a broad dose range (0.01, 0.25 and 5.0 mg/kg) did not produce significant place preference. However, the administration of either 0.25 or 5.0 mg/kg of 7-OH-DPAT 15 min prior to the exposure to morphine (1 mg/kg) prevented the acquisition of a morphine place preference, whereas the 0.01 mg/kg dose of the dopamine receptor agonist was uneffective. In addition, when 7-OH-DPAT was acutely administered 15 min prior to the testing session of an already established morphine place preference, the 0.01 mg/kg dose prevented the expression of this conditioned response. This effect was not observed with either 0.25 and 5.0 mg/kg doses of this dopamine D3 receptor agonist. It was suggested that the different dose related effects of 7-OH-DPAT on the acquisition and expression of morphine place preference might be related to the intrinsic ability of this agonist for interacting with pre- and postsynaptic dopamine D3 receptors located in limbic projecting areas of the mesencephalic dopamine system, although involvement of dopamine D2 receptors cannot be excluded. The pattern of effects seen with 7-OH-DPAT suggests that it may be useful for treating opiate dependence and craving.
本研究调查了全身给予假定的多巴胺D3受体激动剂7-羟基-N，N-二正丙基-2-氨基四氢萘（7-OH-DPAT）对雄性Wistar大鼠吗啡诱导的位置偏爱学习和表达的影响。采用为期3天的条件训练程序，发现7-OH-DPAT在较宽剂量范围（0.01、0.25和5.0mg/kg）内不会产生显著的位置偏爱。然而，在给予吗啡（1mg/kg）前15分钟给予0.25或5.0mg/kg的7-OH-DPAT可阻止吗啡位置偏爱的形成，而0.01mg/kg剂量的多巴胺受体激动剂则无效。此外，当在已建立的吗啡位置偏爱测试前15分钟急性给予7-OH-DPAT时，0.01mg/kg剂量可阻止这种条件反应的表达。该多巴胺D3受体激动剂的0.25和5.0mg/kg剂量未观察到这种效应。研究表明，7-OH-DPAT对吗啡位置偏爱学习和表达的不同剂量相关效应可能与其与中脑多巴胺系统边缘投射区域中突触前和突触后多巴胺D3受体相互作用的内在能力有关，尽管不能排除多巴胺D2受体的参与。7-OH-DPAT的效应模式表明它可能对治疗阿片类药物依赖和渴望有用。
