Panin Francesca, Lintas Alessandra, Diana Marco
"G. Minardi" Laboratory of Cognitive Neuroscience, Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy; Brain Repair Centre, University of Cambridge, CB2 0PY Cambridge, United Kingdom.
"G. Minardi" Laboratory of Cognitive Neuroscience, Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy; Neuroheuristic Research Group, University of Lausanne, Lausanne, Switzerland.
Eur Neuropsychopharmacol. 2014 Jul;24(7):1175-80. doi: 10.1016/j.euroneuro.2014.01.003. Epub 2014 Jan 17.
Stress is well known to affect responsiveness to drugs of abuse and influencing approaching and drug-taking behaviour in both animals and humans. Consistently, in nicotine addicted subjects both negative events and perceived stress levels are reported to increase drug use and facilitate relapse to smoke even after long periods of abstinence. It has been suggested that stressful stimuli may influence the rewarding properties of abused drugs by acting on the dopaminergic mesolimbic system. In line with this hypothesis, a recent microdialysis study in rats has shown that acute restraint stress exposure prevents the nicotine-induced mesolimbic dopaminergic activation in the nucleus accumbens (NAC) shell via a corticosterone-mediated mechanism. In the present study we sought to evaluate the impact of acute restraint stress on nicotine-induced activation of the mesoaccumbal dopaminergic system by extracellular single unit recordings of antidromically-identified NAC shell projecting dopaminergic neurons within the ventral tegmental area (VTA). Nicotine intravenous administration dose-dependently (0.05-0.4mg/kg) stimulated the spontaneous firing and bursting of mesoaccumbal dopaminergic neurons in unstressed rats, as previously reported. By contrast, nicotine failed to increase mesoaccumbal dopaminergic neuron activity in rats previously exposed to 1-h immobilisation stress. Our observations show that acute restraint stress inhibits the response of the mesoaccumbal dopaminergic system to the stimulating properties of nicotine. These findings corroborate the notion that stress reduces the sensitivity to nicotine and suggest that the decreased dopaminergic release in the NAC shell is due to a reduced firing and bursting activity in the VTA.
众所周知，压力会影响对滥用药物的反应，并影响动物和人类的接近及吸毒行为。一直以来，据报道，在尼古丁成瘾者中，负面事件和感知到的压力水平都会增加药物使用，并促进复吸，即使在长时间戒断后也是如此。有人提出，应激刺激可能通过作用于多巴胺能中脑边缘系统来影响滥用药物的奖赏特性。与此假设一致，最近一项对大鼠的微透析研究表明，急性束缚应激暴露通过皮质酮介导的机制阻止了尼古丁诱导的伏隔核（NAC）壳中的中脑边缘多巴胺能激活。在本研究中，我们试图通过对腹侧被盖区（VTA）内逆向鉴定的投射至NAC壳的多巴胺能神经元进行细胞外单单位记录，来评估急性束缚应激对尼古丁诱导的中脑伏隔核多巴胺能系统激活的影响。如先前报道，静脉注射尼古丁（0.05 - 0.4mg/kg）剂量依赖性地刺激了未受应激大鼠中脑伏隔核多巴胺能神经元的自发放电和爆发发放。相比之下，尼古丁未能增加先前暴露于1小时固定应激的大鼠中脑伏隔核多巴胺能神经元的活性。我们的观察结果表明，急性束缚应激会抑制中脑伏隔核多巴胺能系统对尼古丁刺激特性的反应。这些发现证实了压力会降低对尼古丁敏感性的观点，并表明NAC壳中多巴胺能释放减少是由于VTA中发放和爆发发放活动减少所致。
