Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy.
Drug Alcohol Depend. 2013 Jan 1;127(1-3):8-14. doi: 10.1016/j.drugalcdep.2012.06.006. Epub 2012 Jul 17.
Stress affects the responsiveness to nicotine (NIC), by increasing drug use, facilitating relapse and reinstating NIC self administration even after prolonged abstinence. In turn, high corticosterone (CORT) blood levels induced by stress may alter the neurobiological properties of NIC by acting on the dopamine (DA) mesolimbic system.
In this study, we evaluated the effect of exposure to acute restraint stress on NIC-induced stimulation of the mesolimbic DA system of the rat, by studying extracellular DA levels in the nucleus accumbens shell (NAccs) with microdialysis.
NIC intravenous administration (130 μg/kg) increased DA levels in the NAccs in control rats but not in subjects exposed to stress; this latter phenomenon was prevented by blockade of CORT effects with the inhibitor of corticosterone synthesis metirapone (100 mg/kg) or the glucorticoid receptor antagonist mifepristone (150 μmol/kg).
These observations show that exposure to acute stress inhibits the stimulatory response of the mesolimbic DA system to NIC and suggest that this effect is mediated by circulating CORT acting on its receptors. These results may bear relevance in explaining the role played by stressful stimuli in NIC-seeking and taking behavior.
压力通过增加药物使用、促进复发并在长时间戒断后重新开始尼古丁（NIC）自我给药，从而影响对尼古丁的反应。反过来，压力引起的高皮质酮（CORT）血液水平可能通过作用于多巴胺（DA）中脑边缘系统改变 NIC 的神经生物学特性。
在这项研究中，我们通过微透析研究伏隔核壳（NAccs）中的细胞外 DA 水平，评估急性束缚应激暴露对大鼠 NIC 诱导的中脑边缘 DA 系统刺激的影响。
NIC 静脉注射（130μg/kg）增加了对照组大鼠 NAccs 中的 DA 水平，但未增加应激暴露组大鼠的 DA 水平；这一现象可通过皮质酮合成抑制剂米屈肼（100mg/kg）或糖皮质激素受体拮抗剂米非司酮（150μmol/kg）阻断 CORT 作用来预防。
这些观察结果表明，急性应激暴露抑制了中脑边缘 DA 系统对 NIC 的刺激反应，表明这种作用是由循环 CORT 作用于其受体介导的。这些结果可能有助于解释应激刺激在尼古丁寻求和使用行为中所起的作用。
