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The blockade of D1- and D2-like dopamine receptors within the dentate gyrus attenuates food deprivation stress-induced reinstatement of morphine-extinguished conditioned place preference in rats.
Pharmacology Biochemistry and Behavior ( IF 3.3 ) Pub Date : 2020-06-15 , DOI: 10.1016/j.pbb.2020.172967
Roghayeh Mozafari 1 , Shole Jamali 2 , Mahsa Pourhamzeh 1 , Morteza Koruji 1 , Reza Ahadi 1 , Abbas Haghparast 2
Affiliation  

The high rate of relapse to drug abuse is one of the main problems in the treatment of addiction. Stress plays an essential role in relapsing to drug abuse. The present study investigates the role of D1- and D2-like dopamine receptors in the dentate gyrus (DG) of the hippocampus on the reinstatement of morphine (5 mg/kg)-induced conditioned place preference (CPP) both by food deprivation stress (FDS) and a sub-threshold dose of morphine (0.5 mg/kg, s.c.). All the animals in this study experienced pre-test, conditioning, post-test (expression), extinction, and reinstatement phases. The CPP scores of the pre-test and post-test were compared between the groups, and a significant difference between the CPP scores of the pre- and post-test was the criterion for the induction of CPP. Extinction continued for each animal until the calculated score for two consecutive days became the same as the pre-test score. The animals received different doses of SCH-23390 or Sulpiride (0.25, 1 and 4 μg/0.5 μl vehicle), as D1- and D2-like dopamine receptor antagonists, into the DG. After the administration of the antagonists, the animals were deprived of food for 24 h. Then, on the reinstatement day, they received a sub-threshold dose of morphine and afterwards, the conditioning scores were measured. The results demonstrated that the effective doses 50% of SCH-23390 and Sulpiride on the reinstatement induced by FDS and morphine was 1.37 and 2.28 (μg/0.5 μl vehicle per side), respectively. The results also showed that both antagonists can lead to a decrease in morphine reinstatement, and this effect was in a dose-dependent manner. In conclusion, these results indicate that D1- and D2-like dopamine receptors in the DG may be a potential target for preventing relapse to drugs in stressful life conditions.



中文翻译:

齿状回中D1和D2样多巴胺受体的阻滞减弱了大鼠食物剥夺应激诱导的吗啡熄灭条件场所偏好的恢复。

滥用毒品的高复发率是成瘾治疗的主要问题之一。压力在药物滥用复发中起着至关重要的作用。本研究调查了食物缺乏应激对海马齿状回中D1和D2类多巴胺受体在吗啡(5 mg / kg)诱导的条件性位置偏好(CPP)恢复中的作用( FDS)和亚阈值剂量的吗啡(0.5 mg / kg,sc)。该研究中的所有动物都经历了测试前,条件适应,测试后(表达),灭绝和恢复阶段。比较两组之间测试前和测试后的CPP得分,测试前和测试后CPP得分之间的显着差异是诱导CPP的标准。持续灭绝每只动物,直到连续两天的计算得分与测试前得分相同为止。这些动物接受了不同剂量的SCH-23390或舒必利(0.25、1和4μg/ 0.5μl溶媒),作为D1和D2样多巴胺受体拮抗剂进入DG。施用拮抗剂后,将动物剥夺食物24小时。然后,在恢复当天,他们接受了亚阈剂量的吗啡,之后,测量了适应性评分。结果表明,SCH-23390和舒必利对FDS和吗啡诱导的修复的有效剂量分别为1.37和2.28(每侧μg/ 0.5μl载体)。结果还表明,两种拮抗剂均可导致吗啡恢复减少,并且这种作用呈剂量依赖性。

更新日期:2020-06-15
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