Tobin Stephanie, Newman Amy H, Quinn Tammie, Shalev Uri
Department of Psychology, Center for Studies in Behavioral Neurobiology, Concordia University, Montreal, Quebec, Canada.
Int J Neuropsychopharmacol. 2009 Mar;12(2):217-26. doi: 10.1017/S1461145708008778. Epub 2008 Apr 14.
Dopamine has a critical role in drug reinforcement and the reinstatement of drug seeking due to priming or exposure to drug-associated cues. In contrast, the role of dopamine in stress-induced reinstatement is not clear. We have previously demonstrated that acute food deprivation, a clinically relevant stressor, reinstates heroin seeking in rats via a leptin-dependent mechanism. Recent reports have suggested a modulating role for leptin on dopamine transmission and drug-related behaviours. Thus, here we investigated the role of dopamine in acute food deprivation-induced reinstatement of heroin seeking. Rats were trained to self-administer heroin (0.05 mg/kg per infusion) for 10 d. Following training, heroin seeking was extinguished and rats were tested for 48-h food deprivation-induced reinstatement while pretreated with the dopamine D1-, D2-, or D3-like receptor antagonists: SCH 23390 (0.0, 5.0 or 10.0 microg/kg), raclopride (0.0, 50.0 or 100.0 microg/kg) or NGB 2904 (0.0, 0.1 or 5.0 mg/kg), respectively. The dopamine D1-like receptor antagonist, SCH 23390, but neither of the other antagonists, showed a dose-dependent attenuation of food deprivation-induced reinstatement. Our results suggest that acute food deprivation-induced reinstatement may be mediated, at least in part, by activation of the dopamine D1-like receptor.
多巴胺在药物强化以及因启动或接触与药物相关的线索而恢复觅药行为中起着关键作用。相比之下,多巴胺在应激诱导的复吸中的作用尚不清楚。我们之前已经证明,急性食物剥夺,一种与临床相关的应激源,通过一种瘦素依赖机制使大鼠恢复觅求海洛因行为。最近的报告表明瘦素对多巴胺传递和与药物相关的行为具有调节作用。因此,在这里我们研究了多巴胺在急性食物剥夺诱导的海洛因觅求行为恢复中的作用。大鼠被训练自我注射海洛因(每次注射0.05mg/kg),持续10天。训练后,海洛因觅求行为被消除,然后在分别用多巴胺D1、D2或D3样受体拮抗剂预处理的情况下,对大鼠进行48小时食物剥夺诱导的复吸测试:SCH 23390(0.0、5.0或10.0μg/kg)、雷氯必利(0.0、50.0或100.0μg/kg)或NGB 2904(0.0、0.1或5.0mg/kg)。多巴胺D1样受体拮抗剂SCH 23390,但其他拮抗剂均未显示出对食物剥夺诱导的复吸有剂量依赖性的减弱作用。我们的结果表明,急性食物剥夺诱导的复吸可能至少部分是由多巴胺D1样受体的激活介导的。