最新一期PNAS發(fā)表了美國華盛頓大學研究人員最新成果：通過實驗鼠實驗發(fā)現(xiàn)，壓力引起的大腦通路改變能夠調(diào)控大腦特定區(qū)域的血清素,，引起低弱情緒的形成，使得可卡因依賴復發(fā),。
華盛頓大學Michael Bruchas博士介紹說，這項研究的動力來自于他們對壓力如何改變大腦的細胞受體和蛋白信號通路,，并導致情緒變化,，產(chǎn)生憂傷，焦慮以及藥物上癮等比較感興趣,。
普遍的觀念認為藥物上癮是由多巴胺調(diào)控的。研究人員表示,，多巴胺可能仍然是主要的因素,，但他們驚奇的發(fā)現(xiàn)了大腦中縫背核區(qū)域（the dorsal raphe nucleus）的壓力收縮所產(chǎn)生的有害影響。在該區(qū)域,，存在大量利用血清素的神經(jīng)細胞,。這些神經(jīng)元與大腦兩側的伏隔核（nucleus accumbens）的結構有關，而伏隔核在藥物攝入和依賴方面具有重要作用,。此外,，血清素是一種化學神經(jīng)信號，與清醒睡眠周期以及心情有關,。
研究人員解釋說,，在特定的大腦細胞中，存在dynorphin/kappa類鴉片系統(tǒng),。通過反復應力或使用一種化學藥品激活細胞上的受體能將其激活,。該系統(tǒng)的激活使老鼠產(chǎn)生一種條件性厭惡感。研究人員表示,，這種應答是由壓力導致的強啡肽類（dynorphins）釋放引起的,。
在實驗室中，老鼠遇到有侵略性的雄性老鼠表現(xiàn)出沮喪的情緒,。此外,，先前使用過可卡因現(xiàn)在已經(jīng)戒掉的老鼠,，會再次出現(xiàn)藥物需求。
壓力似乎是藥物依賴復發(fā)的一個激發(fā)因素,，會使機體產(chǎn)生不愉快的感覺,，然后會去找一些能夠使它們變得舒服一點的東西，就很有可能會去那些過去能獲得藥物的地方,。
研究人員將繼續(xù)關注大腦中相關通路運作的機制,，這可能有助于加深與壓力，沮喪和上癮相關的大腦機制的理解,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
