Spina Liliana, Fenu Sandro, Longoni Rosanna, Rivas Emilia, Di Chiara Gaetano
Department of Toxicology, Centre of Excellence for Studies on the Neurobiology of Addiction, University of Cagliari and Institute of Neuroscience, Consiglio Nazionale delle Ricerche, Cagliari, Italy.
Psychopharmacology (Berl). 2006 Mar;184(3-4):447-55. doi: 10.1007/s00213-005-0211-4. Epub 2005 Dec 10.
Experimental evidence indicates that the mesolimbic dopamine (DA) pathway innervating the ventral striatum is critically involved in the motivational effects of drug abuse. However, the role of DA transmission of the two main subdivisions of the nucleus accumbens (NAc), the shell and the core, in the motivational properties of nicotine is unknown.
The aim of this study was to investigate the role of DA D1 and D2 receptors of the rat NAc shell and core in the motivational effects of nicotine using a conditioned place preference (CPP) paradigm.
The effect of the intracerebral infusion of DA antagonists specific for DA D1 (SCH 39166) and D2 receptors (L-sulpiride) was studied in a single-trial place-conditioning paradigm with fixed assignment of the drug to the unpreferred compartment.
Nicotine induced significant CPP at the dose of 0.4 and 0.6 mg/kg subcutaneously (s.c.). Intra-NAc shell infusion of SCH 39166 (6.25, 12.5, 25 and 50 ng bilaterally, 10 min before nicotine administration), impaired in a dose-dependent manner the acquisition of CPP by nicotine (0.4 mg/kg s.c.). SCH 39166 failed to affect nicotine CPP when infused into the NAc core. L-sulpiride (25 and 50 ng bilaterally) had no effect on acquisition after intra-Nac shell infusion. SCH 39166 and L-sulpiride were ineffective after infusion in the NAc shell and core 10 min before the test session.
The results indicate that dopamine D1 but not D2 receptors of the NAc shell are specifically involved in the acquisition of nicotine-induced CPP.
实验证据表明，支配腹侧纹状体的中脑边缘多巴胺（DA）通路在药物滥用的动机效应中起关键作用。然而，伏隔核（NAc）两个主要亚区，即壳区和核心区的DA传递在尼古丁动机特性中的作用尚不清楚。
本研究旨在使用条件性位置偏爱（CPP）范式，研究大鼠NAc壳区和核心区的DA D1和D2受体在尼古丁动机效应中的作用。
在单次试验位置条件化范式中，将药物固定分配到非偏好隔室，研究脑内注射对DA D1（SCH 39166）和D2受体（L-舒必利）具有特异性的DA拮抗剂的效果。
尼古丁皮下注射剂量为0.4和0.6 mg/kg时可诱导显著的CPP。在NAc壳区内双侧注射SCH 39166（6.25、12.5、25和50 ng，尼古丁给药前10分钟），以剂量依赖方式损害尼古丁（0.4 mg/kg皮下注射）诱导的CPP获得。向NAc核心区内注射SCH 39166时不影响尼古丁CPP。L-舒必利（双侧25和50 ng）在向NAc壳区内注射后对CPP获得无影响。在测试前10分钟向NAc壳区和核心区内注射SCH 39166和L-舒必利均无效。
结果表明，NAc壳区的多巴胺D1而非D2受体特异性参与尼古丁诱导的CPP的获得。
