Zarrindast Mohammad-Reza, Azami Bibi-Nasrin, Rostami Parvin, Rezayof Ameneh
Department of Pharmacology and Iranian National Center for Addiction Studies, School of Medicine, Tehran University of Medical Sciences, PO Box 13145-784, Tehran, Iran.
Behav Brain Res. 2006 May 15;169(2):248-55. doi: 10.1016/j.bbr.2006.01.011. Epub 2006 Feb 10.
In the present study, the effects of repeated intra nucleus accumbens (intra-NAc) injections of dopamine receptor agents on morphine-induced conditioned place preference (CPP) in rats were investigated by using an unbiased 3-days schedule of place conditioning design. The animals receiving once daily subcutaneous (s.c.) injections of morphine (0.5-7.5mg/kg) or saline (1.0 ml/kg, s.c.) showed a significant place preference in a dose-dependent manner. The maximum response was observed with 5mg/kg of the opioid. Three days intra-NAc injections of apomorphine (0.5 and 1 microg/rat) followed by 5 days free of the drug, increased or decreased, respectively CPP induced by the lower dose of morphine (0.5mg/kg, s.c.). Morphine-induced CPP was also significantly increased in the animals that had previously received the 3-days intra-NAc injections of SKF 38393 (4 and 8 microg/rat) or quinpirole (2 and 4 microg/rat, intra-NAc). The CPP induced by a higher dose of morphine (5mg/kg, s.c.) was significantly decreased in the animals that had previously received the 3-days SCH 23390 (0.005 and 0.01 microg/rat; intra-NAc). On the other hand, the CPP induced by morphine (5mg/kg, s.c.) was significantly increased in the animals that had previously received the 3-days sulpiride administration (5 microg/rat, intra-NAc). The 3-days administration of apomorphine, SKF 38393 or quinpirole, but not SCH 23390 and sulpiride reduced the locomotor activity in the test session. It is concluded that repeated injections of dopamine receptors agents followed by 5 days free of the drugs in the NAc can affect morphine reward.
在本研究中，通过使用无偏倚的3天位置条件反射设计方案，研究了反复向大鼠伏隔核内注射多巴胺受体药物对吗啡诱导的条件性位置偏爱（CPP）的影响。每天接受一次皮下注射吗啡（0.5 - 7.5mg/kg）或生理盐水（1.0ml/kg，皮下注射）的动物呈现出剂量依赖性的显著位置偏爱。在使用5mg/kg阿片类药物时观察到最大反应。向伏隔核内连续3天注射阿扑吗啡（0.5和1μg/只大鼠），随后停药5天，分别增强或减弱了低剂量吗啡（0.5mg/kg，皮下注射）诱导的CPP。在先前接受伏隔核内连续3天注射SKF 38393（4和8μg/只大鼠）或喹吡罗（2和4μg/只大鼠，伏隔核内注射）的动物中，吗啡诱导的CPP也显著增强。在先前接受伏隔核内连续3天注射SCH 23390（0.005和0.01μg/只大鼠）的动物中，高剂量吗啡（5mg/kg，皮下注射）诱导的CPP显著降低。另一方面，在先前接受伏隔核内连续3天注射舒必利（5μg/只大鼠）的动物中，吗啡（5mg/kg，皮下注射）诱导的CPP显著增强。在测试阶段，连续3天给予阿扑吗啡、SKF 38393或喹吡罗，但不包括SCH 23390和舒必利，会降低运动活性。得出的结论是，在伏隔核内反复注射多巴胺受体药物，随后停药5天，可影响吗啡奖赏。
