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飲酒文化是任何文化都不可或缺的一部分，我泱泱華夏文明更甚。凡是才子都與酒有不解之緣。
風(fēng)流才子如李白：天子呼來不上船，自稱臣是酒中仙。
唐寅：但愿長醉花酒間，不愿鞠躬車馬前。
還有“太守醉也”的歐陽修，“把酒問青天”的蘇東坡，更毋庸提“酒仙”劉伶，“酒鬼”李賀，“酒圣”杜甫。酒俗文化源遠(yuǎn)流長，甲骨文中就有跡可循。人類自從有了發(fā)酵技術(shù)就沉迷于酒精，這其中固然有社會文化因素，喜要喝酒（烹羊宰牛且為樂 會須一飲三百杯）、悲也要喝酒（抽刀斷水水更流 舉杯銷愁愁更愁），但也許沒有想到的是，飲酒成性還有生物學(xué)因素?？磥砭埔膊皇悄阆牒认牒染湍芎龋幌牒炔幌牒染湍軗]手bye bye，大步走開。
愛飲酒者多，但酗酒者（即被酒精捆綁，無法自由選擇其它消遣模式者）大概穩(wěn)定地占喝酒人數(shù)的15%。為了模擬酗酒，瑞典的一隊(duì)科學(xué)家用620只大鼠做實(shí)驗(yàn)。大鼠和人一樣，偏愛甜食、愛喝糖水。學(xué)者們先用十周左右的時(shí)間讓大鼠自行熟悉和飲用20%的酒精，然后同時(shí)將糖水和酒精放在大鼠籠子里。大部分大鼠在有了糖水的選擇后，都不再飲用酒精，只有極少的一部分（95/620）持續(xù)飲用酒精。對于這95只“上癮”的大鼠，科學(xué)家們發(fā)現(xiàn)，即使在酒精里摻入大鼠們不喜的一種苦澀的物質(zhì)醌、或者在他們每次喝酒時(shí)電擊腳掌，仍然無法阻擋“上癮”大鼠一顆勇往直前的心。
觥籌影中死，做鬼也風(fēng)流。
難喝不能阻擋我、疼痛不能阻擋我、妻離子散家破人亡不能阻擋我。你便是落了我牙、歪了我嘴、瘸了我腿、折了我手，天賜與我這幾般兒歹癥候，尚兀自不肯休。則除是閻王親自喚，神鬼自來勾，三魂歸地府，七魄喪冥幽，天那，那其間方能罷酒?。?）
這些大鼠到底怎么了？它們的大腦與喝糖水的大鼠有什么不一樣？
科學(xué)家們把愛喝酒和不愛喝酒的大鼠大腦不同部位的基因表達(dá)進(jìn)行了對比，發(fā)現(xiàn)很多明顯的區(qū)別位于大腦杏仁核！杏仁核是大腦中負(fù)責(zé)產(chǎn)生、識別和調(diào)整情緒、以及控制學(xué)習(xí)和記憶的部位。而這其中表達(dá)量變化最大的就是GABA傳導(dǎo)通路中的GABA受體。
GABA即r-氨基丁酸，是神經(jīng)傳導(dǎo)中一個(gè)重要的因子，缺乏GABA會使人失眠、恐慌、易怒。日常食用的普洱茶、泡菜，都是GABA的重要來源。在神經(jīng)傳導(dǎo)的過程中，神經(jīng)元在刺激下把GABA釋放到細(xì)胞間。傳導(dǎo)結(jié)束后，細(xì)胞間的GABA則需要被迅速清除。而細(xì)胞間并不存在可以分解GABA的酶，它們只能通過GABA通道被重新運(yùn)送回神經(jīng)細(xì)胞內(nèi)?？上攵?，GABA受體和通道的減少會影響GABA迅速有效的消除。
研究者們發(fā)現(xiàn)，在酗酒的大鼠中，負(fù)責(zé)轉(zhuǎn)運(yùn)GABA的GAT-3轉(zhuǎn)運(yùn)體大量減少，造成GABA在細(xì)胞間的堆積。而奇妙的是，當(dāng)人為的減少愛喝糖水的大鼠大腦中的GABA轉(zhuǎn)運(yùn)體時(shí)，它們也突然莫名的愛上了酒精！
這個(gè)實(shí)驗(yàn)的巧妙之處在于：成功的模擬了酗酒作為一種病的臨床表現(xiàn)和概率，也似乎找到了原因 — GABA轉(zhuǎn)運(yùn)體的減少。原來人生的好多選擇都是虛假的，看似自主選擇，其實(shí)愛好與否、甚至上癮與否，早就寫在我們的基因里。
人類有時(shí)其實(shí)是傲慢的。在我們學(xué)會了用大腦思考抽象的、哲學(xué)的問題以后，我們開始鄙夷和摒棄自己的身體。殊不知一些我們自以為是自主的、自由的想法，實(shí)則仍然是在肉體的操控之下。這也不是第一個(gè)生物機(jī)能決定行為的例子了，一些病毒和寄生蟲，不但可以影響身體健康，還能左右思維模式！最廣為人知的例子大概就是弓形蟲了。弓形蟲的宿主是貓，只有在貓的體內(nèi)才能繁殖，但可以短暫的寄居在人或者老鼠的身體中。貓捉老鼠、老鼠怕貓是亙古不變的真理。意料不到的是，當(dāng)老鼠被弓形蟲感染以后，神奇的事情發(fā)生了：老鼠不但不害怕貓，反而愛上了貓尿的味道！大無畏地把自己送入貓的口中，而目的只有一個(gè)：弓形蟲需要重回貓的身體里進(jìn)行繁殖。人類（非孕婦）感染弓形蟲似乎沒有特別明顯的癥狀，實(shí)則是因?yàn)樵诂F(xiàn)代社會，一個(gè)大活人被貓吃掉的概率也太小了。但是人類的遠(yuǎn)親猩猩在感染了弓形蟲以后，會莫名愛上豹子的體味，而豹子則是猩猩在自然界中少有的天敵。所以如果有一天突然愛上了鏟屎官的工作，十有八九是病毒在思考。
我想這是一個(gè)很值得思考的哲學(xué)問題。我們的身體到底在多大程度上控制我們的行為？缺少GABA轉(zhuǎn)運(yùn)體相對來說更容易飲酒上癮，但這也不是必然。環(huán)境因素（是否經(jīng)常接觸酒精）、性格因素（是否有極強(qiáng)的自控力）等都和生物學(xué)因素交雜在一起，成就了五彩斑斕的人生。或許真正的強(qiáng)大，是直面和克服自己的軟弱，是明知不可為而為之。
不知不可為而為之，愚人也；知其不可為而不為，賢人也；知其不可為而為之，圣人也。（2）
最后，我想這也告訴我們，作為旁觀者，看到“癮君子”，或許我們應(yīng)該更少論斷他們的家庭、經(jīng)歷、自制力和人格，而更多的去體恤他們?nèi)怏w上的軟弱。
對酒當(dāng)歌，人生幾何？譬如朝露，去日苦多。
快意的人生需要酒精的點(diǎn)綴，而非綁架。
Addicted or afflicted?
When my husband and I first started dating, we took a leisurely stroll along a river in southwest China one summer evening. It was one of those lazy, perfect summer dusks, with children calling out and laughing as they swam like fishes in the river, and the hot, somewhat humid summer air settled like a warm but breathable shawl about one's shoulders. We stopped by a food cart that sold shaved ice and cold beer and I bought one of each. As we sat on a bench overlooking the river and the last traces of the sunset, I offered him the bottle of teeth-punchingly cold and soul-refreshing beer, to which he said, "sorry, I don't drink."
I believe that was the singular shakiest moment of our entire courtship.
One year into our marriage, I made for him a bottle opener for Valentine's Day. On it was written, "Happy Valentine's Day! - From 'The Reason You Drink' ". I believe that this is true on multiple levels, and that a heartfelt thank you is long overdue.
I love my drinks on weekends, my glass of wine, my gin and tonic, my occasional beer, and even the rarer shots of Chinese baijiu. Personally I feel it makes the rest and celebration of the weekends more wholesome. I am far from alone in my love of alcohol. It appears that in 2016, 5 billion liters of the beloved Chinese baijiu was sold alone. However, while the love of alcohol is widespread (it is the oldest recreational drug, after all), it appears that we may have less of a choice than we think when it comes to how much we love it. For some people (approximately 15% of the drinking population), the love of alcohol develops into a bigger problem: addiction.
A team of Swedish and American scientists tried to model human alcohol choice and addiction in lab rats. After training rats to self-administer 20% of alcohol for about 10 weeks, they were then given mutually exclusive choices between alcohol and sugar water. Like humans, rats have evolved to have a "sweet tooth", and when given the choice, most quickly chose sugar over alcohol. The experiment was repeated multiple times, and scientists found that 95 out of 620 (15.3%) rats consistently chose alcohol despite having a sugar alternative. These alcohol-preferring rats doggedly continued to choose alcohol even when faced with strong deterrents. They didn't care if the alcohol was adulterated with quinine (a bitter drug) to highly aversive concentrations. They ignored the pain from an electrical foot shock every time they drank. They pursued the drink with no fear of consequences. In other words, they were addicted.
So what's different about alcohol-preferring (AP) rats? Are their brains somehow wired differently? Scientists took sections from different regions of the AP rats' brains and compared gene expression patterns to the same brain regions of the non-addicted rats. Interestingly, a lot of the differences were clustered in the amygdala. The amygdala is an almond shaped part of the brain known to be associated with emotional responses such as anxiety, aggression and fear, as well as memory and learning. One of the genes most affected was a GABA transporter, GAT-3.
GABA -gamma-Aminobutyric acid - is an inhibitory neurotransmitter. It can reduce neuronal excitability, thereby decreasing stress and improving rest. When neurons fire, GABA is released into the extracellular space. It then needs to be cleared away from outside of the cells to create a sufficient GABA gradient in preparation for the next round of firing. However, no enzymes exist in the extracellular space to degrade GABA. Therefore, it must rely on transporters to relocate it back into the cell. Decrease of the GABA transporter GAT-3, as seen in the brains of AP rats, results in dysfunctional GABA clearance. Even more interestingly, when scientists manipulate the amount of GAT-3 inside the brains of non-addicted rats, these rats start showing a preference for alcohol over sugar! This suggests that low levels of GABA transporters might be the reason that AP rats became addicted in the first place.
Our daily activities and choices are dictated by both our bodies and our minds. We'd like to think that for non-survival-essential choices such as the pursuit of pleasure, our minds play a bigger role than our bodies. Certainly, we'd like to believe that we are not mere creatures controlled by the whims of the physical. However, this is not the first example that we have fewer choices in life than we'd like to think. A well known mind twister is the parasite Toxoplasma gondii, which resides and breeds in cats but can infect both people and mice if they come into contact with cat feces. Mice make themselves scarce when they are in cat territory, but when they become infected by Toxoplasma gondii, they become fatally attracted to the smell of cats. Why? Because the parasite needs to make it back into its host in order to multiply and complete its life cycle. When humans get infected, the symptoms are harder to recognize, as the chances of any person being eaten by felines is infinitesimally small (now). However, when our primate cousins chimpanzees become infected, they become attracted to the smell of leopard urine, their only known predator in nature. So if you suddenly develop a love for scooping the litter, better think twice about whether your motivation comes from affection for your furry companion, or just a parasite twisting your mind!
The knowledge that some of our behavior is pre-written in our genes or in biology helps us in multiple ways. First of all it definitely lends us a tool to deal with unwelcome behavior. For example, in this case, elevating GAT-3 expression may alleviate alcohol addiction. Secondly, in this day and age, when we have progressed beyond judging people by their looks or socioeconomic status, but spare no mercy when it comes to judging people's life choices, perhaps it is important to recognize that some behaviors are rooted in pre-existing genetic and biological conditions. Of course, this cuts two ways. When we are the ones afflicted, knowing that we are biologically more susceptible may aid us in making wise decisions to err on the side of caution and exercise control when it comes to drinking. However, when those around us are affected, perhaps we should cut them some slack and admit that not all things can be controlled, despite our best intentions.
In Shakespeare's Othello, when the jealous Iago tries to persuade Cassio to drink while on duty, hoping to bring about his demotion, Cassio? laments, "I have very poor and unhappy brains for drinking. I could well wish courtesy would invent some other custom of entertainment." I hope, for all our sakes, that when courtesy does invent it, we can all be free to choose it.
References
Eric Augier, Estelle Barbier, Russell S. Dulman, Valentina Licheri, Ga?lle Augier, Esi Domi, Riccardo Barchiesi, Sean Farris, Daniel N?tt, R. Dayne Mayfield, Louise Adermark, Markus Heilig. A molecular mechanism for choosing alcohol over an alternative reward. Science, 2018; 360 (6395): 1321 DOI: 10.1126/science.aao1157
(1) 關(guān)漢卿 《不伏老》
（2） 張岱 《四書遇》
(3) RAINER SPANAGEL Aberrant choice behavior in alcoholism. SCIENCE22 JUN 2018 : 1298-1299
