最新一期PNAS发表了美国华盛顿大学研究人员最新成果：通过实验鼠实验发现，压力引起的大脑通路改变能够调控大脑特定区域的血清素，引起低弱情绪的形成，使得可卡因依赖复发。
华盛顿大学Michael Bruchas博士介绍说，这项研究的动力来自于他们对压力如何改变大脑的细胞受体和蛋白信号通路，并导致情绪变化，产生忧伤，焦虑以及药物上瘾等比较感兴趣。
普遍的观念认为药物上瘾是由多巴胺调控的。研究人员表示，多巴胺可能仍然是主要的因素，但他们惊奇的发现了大脑中缝背核区域（the dorsal raphe nucleus）的压力收缩所产生的有害影响。在该区域，存在大量利用血清素的神经细胞。这些神经元与大脑两侧的伏隔核（nucleus accumbens）的结构有关，而伏隔核在药物摄入和依赖方面具有重要作用。此外，血清素是一种化学神经信号，与清醒睡眠周期以及心情有关。
研究人员解释说，在特定的大脑细胞中，存在dynorphin/kappa类鸦片系统。通过反复应力或使用一种化学药品激活细胞上的受体能将其激活。该系统的激活使老鼠产生一种条件性厌恶感。研究人员表示，这种应答是由压力导致的强啡肽类（dynorphins）释放引起的。
在实验室中，老鼠遇到有侵略性的雄性老鼠表现出沮丧的情绪。此外，先前使用过可卡因现在已经戒掉的老鼠，会再次出现药物需求。
压力似乎是药物依赖复发的一个激发因素，会使机体产生不愉快的感觉，然后会去找一些能够使它们变得舒服一点的东西，就很有可能会去那些过去能获得药物的地方。
研究人员将继续关注大脑中相关通路运作的机制，这可能有助于加深与压力，沮丧和上瘾相关的大脑机制的理解。（生物谷Bioon.com）
生物谷推荐原始出处：
PNAS October 28, 2009, doi: 10.1073/pnas.0910705106
Activation of the kappa opioid receptor in the dorsal raphe nucleus mediates the aversive effects of stress and reinstates drug seeking
Benjamin B. Landa,b,1, Michael R. Bruchasa,1, Selena Schattauera, William J. Giardinoa, Megumi Aitaa, Daniel Messingera, Thomas S. Hnaskob,c, Richard D. Palmiterb,c,d,2 and Charles Chavkina,b,2
aDepartment of Pharmacology,
bGraduate Program in Neurobiology and Behavior,
cDepartment of Biochemistry, and
dHoward Hughes Medical Institute, University of Washington, Seattle, WA 98195
Although stress has profound effects on motivated behavior, the underlying mechanisms responsible are incompletely understood. In this study we elucidate a functional pathway in mouse brain that encodes the aversive effects of stress and mediates stress-induced reinstatement of cocaine place preference (CPP). Activation of the dynorphin/kappa opioid receptor (KOR) system by either repeated stress or agonist produces conditioned place aversion (CPA). Because KOR inhibition of dopamine release in the mesolimbic pathway has been proposed to mediate the dysphoria underlying this response, we tested dopamine-deficient mice in this study and found that KOR agonist in these mice still produced CPA. However, inactivation of serotonergic KORs by injection of the KOR antagonist norBNI into the dorsal raphe nucleus (DRN), blocked aversive responses to the KOR agonist U50,488 and blocked stress-induced reinstatement of CPP. KOR knockout (KO) mice did not develop CPA to U50,488; however, lentiviral re-expression of KOR in the DRN of KOR KO mice restored place aversion. In contrast, lentiviral expression in DRN of a mutated form of KOR that fails to activate p38 MAPK required for KOR-dependent aversion, did not restore place aversion. DRN serotonergic neurons project broadly throughout the brain, but the inactivation of KOR in the nucleus accumbens (NAc) coupled with viral re-expression in the DRN of KOR KO mice demonstrated that aversion was encoded by a DRN to NAc projection. These results suggest that the adverse effects of stress may converge on the serotonergic system and offers an approach to controlling stress-induced dysphoria and relapse.
