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[[Alcohol]], specifically [[ethanol]], is a potent [[central nervous system]] [[depressant]], with a range of [[side effects]]. The amount and circumstances of consumption play a large part in determining the extent of [[intoxication]]; e.g., consuming alcohol after a heavy meal is less likely to produce visible signs of intoxication than consumption on an empty stomach. [[Hydration]] also plays a role, especially in determining the extent of [[hangover]]s. The concentration of alcohol in blood is usually given by the "[[blood alcohol content]]".
 
[[Alcohol]], specifically [[ethanol]], is a potent [[central nervous system]] [[depressant]], with a range of [[side effects]]. The amount and circumstances of consumption play a large part in determining the extent of [[intoxication]]; e.g., consuming alcohol after a heavy meal is less likely to produce visible signs of intoxication than consumption on an empty stomach. [[Hydration]] also plays a role, especially in determining the extent of [[hangover]]s. The concentration of alcohol in blood is usually given by the "[[blood alcohol content]]".
   
Alcohol has a [[biphasic]] effect on the body, which is to say that its effects change over time. Initially, alcohol generally produces feelings of relaxation and cheerfulness, but further consumption can lead to blurred vision and coordination problems. [[Cell membrane]]s are highly permeable to alcohol, so once alcohol is in the bloodstream it can diffuse into nearly every biological tissue of the body. After [[binge drinking|excessive drinking]], [[unconsciousness]] can occur and extreme levels of consumption can lead to [http://effects-of-alcohol.org/alcohol-poisoning alcohol poisoning] and [[death]] (a concentration in the blood stream of 0.55% will [[LD50|kill half of those affected]]). Death can also be caused by asphyxiation when vomit, a frequent result of over-consumption, blocks the [[trachea]] and the individual is too inebriated to respond. An appropriate first aid response to an unconscious, drunken person is to place them in the recovery position.
+
Alcohol has a [[biphasic]] effect on the body, which is to say that its effects change over time. Initially, alcohol generally produces feelings of relaxation and cheerfulness, but further consumption can lead to blurred vision and coordination problems. [[Cell membrane]]s are highly permeable to alcohol, so once alcohol is in the bloodstream it can diffuse into nearly every biological tissue of the body. After [[binge drinking|excessive drinking]], [[unconsciousness]] can occur and extreme levels of consumption can lead to alcohol poisoning and [[death]] (a concentration in the blood stream of 0.55% will [[LD50|kill half of those affected]]). Death can also be caused by asphyxiation when vomit, a frequent result of over-consumption, blocks the [[trachea]] and the individual is too inebriated to respond. An appropriate first aid response to an unconscious, drunken person is to place them in the recovery position.
   
 
Intoxication frequently leads to a lowering of one's [[inhibition]]s, and intoxicated people will do things they would not do while sober, often ignoring social, moral, and legal considerations.
 
Intoxication frequently leads to a lowering of one's [[inhibition]]s, and intoxicated people will do things they would not do while sober, often ignoring social, moral, and legal considerations.
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CachacaDivininha

Bottles of cachaça, a Brazilian alcoholic beverage.

The effects of alcohol on the human body can take several forms.

Alcohol, specifically ethanol, is a potent central nervous system depressant, with a range of side effects. The amount and circumstances of consumption play a large part in determining the extent of intoxication; e.g., consuming alcohol after a heavy meal is less likely to produce visible signs of intoxication than consumption on an empty stomach. Hydration also plays a role, especially in determining the extent of hangovers. The concentration of alcohol in blood is usually given by the "blood alcohol content".

Alcohol has a biphasic effect on the body, which is to say that its effects change over time. Initially, alcohol generally produces feelings of relaxation and cheerfulness, but further consumption can lead to blurred vision and coordination problems. Cell membranes are highly permeable to alcohol, so once alcohol is in the bloodstream it can diffuse into nearly every biological tissue of the body. After excessive drinking, unconsciousness can occur and extreme levels of consumption can lead to alcohol poisoning and death (a concentration in the blood stream of 0.55% will kill half of those affected). Death can also be caused by asphyxiation when vomit, a frequent result of over-consumption, blocks the trachea and the individual is too inebriated to respond. An appropriate first aid response to an unconscious, drunken person is to place them in the recovery position.

Intoxication frequently leads to a lowering of one's inhibitions, and intoxicated people will do things they would not do while sober, often ignoring social, moral, and legal considerations.

Alcohol psychology

Alcohol use
Alcohol abuse
Alcohol consumption and health
Treatment of alcohol problems

Action on the brain Edit

File:Emandheather.jpg

Ethanol is quickly absorbed into the bloodstream and reaches the brain. As a small molecule, it is able to cross the blood-brain barrier. The molecular targets of alcohols actions remain essentially unidentified, although many targets have been suggested, including ion channels[1] and intracellular signaling molecules. Alcohol works on the GABA system at the synaptic level, and it has a rapid onset of action. Essentially, it causes the GABA receptor, which is an ion channel, to remain open longer than it does without the addition of ethanol into the synaptic cleft (the space between two neurons, or brain cells). This causes more negatively charged particles to enter brain cells than would under normal conditions. The overall effect is to slow the functional processes of the brain cell. GABA is commonly known as the brain's "brake" mechanism.

Ethanol's inhibiotry effects also target glutamate, an excitory neurotransmitter. Glutamate affects neurons by allowing them to fire easier, creating more active tissue. Ethanol consumption leads to the redution of glutamate activity of the N-methyl-D-asparate or NMDA class of glutamate receptors.

Blackouts Edit

Main article: Blackout (Alcohol Related Amnesia)

"Blacking out" or blackouts (a form of anterograde amnesia) are a common problem usually associated with heavy drinking. They are characterized by a person's inability to recall events which occurred during the period of blacking out.

Carcinogenic effects Edit

Main article: Alcohol and cancer

The International Agency for Research on Cancer (Centre International de Recherche sur le Cancer) of the World Health Organization has classified alcohol as a Group 1 carcinogen. Its evaluation states, "There is sufficient evidence for the carcinogenicity of alcoholic beverages in humans.… Alcoholic beverages are carcinogenic to humans (Group 1)."[2]

The U.S. National Institute on Alcohol Abuse and Alcoholism (NIAAA) reports that "Although there is no evidence that alcohol itself is a carcinogen, alcohol may act as a cocarcinogen by enhancing the carcinogenic effects of other chemicals. For example, studies indicate that alcohol enhances tobacco's ability to stimulate tumor formation in rats.[3] In humans, the risk for mouth, tracheal, and esophageal cancer is 35 times greater for people who both smoke and drink than for people who neither smoke nor drink,[4] implying a cocarcinogenic interaction between alcohol and tobacco-related carcinogens."[5]

"Studies have suggested that high concentrations of acetaldehyde, which is produced as the body breaks down ethanol, could damage DNA in healthy cells. … Researchers at the National Institute on Alcohol Abuse and Alcoholism in Bethesda, Maryland, have added weight to this idea by showing that the damage occurs at concentrations of acetaldehyde similar to those in saliva and the gastrointestinal tract while people drink alcohol. Acetaldehyde appears to react with polyamines - naturally occurring compounds essential for cell growth - to create a particularly dangerous type of mutagenic DNA base called a Cr-Pdg adduct…"[6]

The strongest link between alcohol and cancer involves cancers of the upper digestive tract, including the esophagus, the mouth, the pharynx, and the larynx. Less consistent data link alcohol consumption and cancers of the liver, breast, and colon.

Upper digestive tract. Chronic heavy drinkers have a higher incidence of esophageal cancer than does the general population. The risk appears to increase as alcohol consumption increases. An estimated 75% of esophageal cancers in the United States are attributable to chronic, excessive alcohol consumption.

Nearly 50% of cancers of the mouth, pharynx, and larynx are associated with heavy drinking. According to mid-1980s U.S. case-control study, people who consumed an average of more than four drinks per day incurred a ninefold increase in risk of oral and pharyngeal cancer, while there was about a fourfold increase in risk associated with smoking two or more packs of cigarettes per day. Heavy drinkers who also were heavy smokers experienced a greater than 36-fold excess compared to abstainers from both products.

Liver. Prolonged, heavy drinking has been associated in many cases with primary liver cancer. However, it is liver cirrhosis, whether caused by alcohol or another factor, that is thought to induce the cancer. In the United States, liver cancer is relatively uncommon, afflicting approximately 2 people per 100,000, but excessive alcohol consumption is linked to as many as 36% of these cases by some investigators.

Metabolism of alcohol and action on the liver Edit

The liver breaks down alcohols into acetaldehyde by the enzyme alcohol dehydrogenase, and then into acetic acid by the enzyme acetaldehyde dehydrogenase. Next, the acetate is converted into fats or carbon dioxide and water. The fats are mostly deposited locally which, according to some,[attribution needed] leads to the characteristic "beer belly".[How to reference and link to summary or text] Chronic drinkers, however, so tax this metabolic pathway that things go awry: fatty acids build up as plaques in the capillaries around liver cells and those cells begin to die, which leads to the liver disease cirrhosis. The liver is part of the body's filtration system and if it is damaged then certain toxins build up, thus leading to symptoms of jaundice.

The alcohol dehydrogenase of women is less effective than that of men. The percentage of water in women's bodies is less than that of men. Therefore, the alcohol has less volume to dissolve in, leading to a higher blood alcohol concentration when the same amount of alcohol is ingested. This contributes to the fact that women become intoxicated more quickly than men. Also contributing is the fact that men have a more active first-pass metabolism of alcohol in the stomach and small intestine.[How to reference and link to summary or text]

Some people have a genetic mutation in their acetaldehyde dehydrogenase gene, resulting in less potent acetaldehyde dehydrogenase. This leads to a buildup of acetaldehyde after alcohol consumption, causing the alcohol flush reaction with hangover-like symptoms such as flushing, nausea, and dizziness. These people are unable to drink much alcohol before feeling sick, and are therefore less susceptible to alcoholism.[7][8] This adverse reaction can be artificially reproduced by drugs such as disulfiram, which are used to treat chronic alcoholism by inducing an acute sensitivity to alcohol.

Dehydration Edit

Consumption of ethanol has a rapid diuretic effect, meaning that more urine than usual is produced, since ethanol inhibits the production of antidiuretic hormone.

Overconsumption can therefore lead to dehydration (the loss of water).

Hangover Edit

Main article: Hangover

A common after-effect of ethanol intoxication is the unpleasant sensation known as hangover, which is partly due to the dehydrating effect of ethanol. Hangover symptoms include dry mouth, headache, nausea, and sensitivity to light and noise. These symptoms are partly due to the toxic acetaldehyde produced from alcohol by alcohol dehydrogenase, and partly due to general dehydration. The dehydration portion of the hangover effect can be mitigated by drinking plenty of water between and after alcoholic drinks. Other components of the hangover are thought to come from the various other chemicals in an alcoholic drink, such as the tannins in red wine, and the results of various metabolic processes of alcohol in the body, but few scientific studies have attempted to verify this. Consuming water between drinks and before bed is the best way to prevent or lessen the effects of a hangover.

Beneficial effects of alcoholEdit

See also: Alcohol consumption and health

The World Health Organization (WHO) reports that there is convincing evidence that "low to moderate alcohol intake" results in a decreased risk of coronary heart disease.[9] However, the WHO cautions that "other cardiovascular and health risks associated with alcohol do not favour a general recommendation for its use."[10]

Also it has been suggested that moderate consumption of alcohol can reduce the risk of dementia, facilitate memory and learning,[11] and even improve IQ scores.[12] Moderate drinkers tend to have better health and live longer than those who abstain from alcohol or are heavy drinkers, but this average difference is largely explained by the fact that a large fraction of abstainers are ex-alcoholics or those who have health problems or take drugs that preclude the use of alcohol, and has far less relevance to those who abstain for other reasons.[13]

Effects by doseEdit

Different concentrations of alcohol in the human body have different effects on the subject. The following lists the effects of alcohol on the body, depending on the blood alcohol concentration or BAC.[14][15][16] Also, tolerance varies considerably between individuals.

Please note: the BAC percentages provided below are just estimates and used for illustrative purposes only. They are not meant to be an exhaustive reference; please refer to a healthcare professional if more information is needed.
  • Euphoria (BAC = 0.03 to 0.12 %)
    • Subject may experience an overall improvement in mood and possible euphoria.
    • They may become more self-confident or daring.
    • Their attention span shortens. They may look flushed.
    • Their judgement is not as good — they may express the first thought that comes to mind, rather than an appropriate comment for the given situation.
    • They have trouble with fine movements, such as writing or signing their name.
  • Lethargy (BAC = 0.09 to 0.25 %)
    • Subject may become sleepy
    • They have trouble understanding or remembering things, even recent events. They do not react to situations as quickly.
    • Their body movements are uncoordinated; they begin to lose their balance easily, stumbling; walking is not stable.
    • Their vision becomes blurry. They may have trouble sensing things (hearing, tasting, feeling, etc.).
  • Confusion (BAC = 0.18 to 0.30 %)
    • Profound confusion — uncertain where they are or what they are doing. Dizziness and staggering occur.
    • Heightened emotional state — aggressive, withdrawn, or overly affectionate. Vision, speech, and awareness are impaired.
    • Poor coordination and pain response. Nausea and vomiting often occur.
  • Stupor (BAC = 0.25 to 0.40 %)
    • Movement severely impaired; lapses in and out of consciousness.
    • Subjects can slip into a coma; will become completely unaware of surroundings, time passage, and actions.
    • Risk of death is very high due to alcohol poisoning and/or pulmonary aspiration of vomit while unconscious.
  • Coma (BAC = 0.35 to 0.50 %)
    • Unconsciousness sets in.
    • Reflexes are depressed (i.e., pupils do not respond appropriately to changes in light).
    • Breathing is slower and more shallow. Heart rate drops. Death usually occurs at levels in this range.

Moderate doses Edit

Although alcohol is typically thought of purely as a depressant, at low concentrations it can actually stimulate certain areas of the brain. Alcohol sensitises the N-methyl-D-aspartate (NMDA) system of the brain, making it more receptive to the neurotransmitter glutamate. Stimulated areas include the cortex, hippocampus and nucleus accumbens, which are responsible for thinking and pleasure seeking. Another one of alcohol's agreeable effects is body relaxation, possibly caused by heightened alpha brain waves surging across the brain. Alpha waves are observed (with the aid of EEGs) when the body is relaxed. Heightened pulses are thought to correspond to higher levels of enjoyment.

A well-known side effect of alcohol is lowering inhibitions. Areas of the brain responsible for planning and motor learning are dulled. A related effect, caused by even low levels of alcohol, is the tendency for people to become more animated in speech and movement. This is due to increased metabolism in areas of the brain associated with movement, such as the nigrostriatal pathway. This causes reward systems in the brain to become more active, and combined with reduced understanding of the consequences of their behavior, can induce people to behave in an uncharacteristically loud and cheerful manner.

Behavioural changes associated with drunkenness are, to some degree, contextual. A scientific study found that people drinking in a social setting significantly and dramatically altered their behaviour immediately after the first sip of alcohol, well before the chemical itself could have filtered through to the nervous system. Likewise, people consuming non-alcoholic drinks often exhibit drunk-like behaviour on a par with their alcohol-drinking companions even though their own drinks contained no alcohol whatsoever.

Excessive doses Edit

The effect alcohol has on the NMDA receptors, earlier responsible for pleasurable stimulation, turns from a blessing to a curse if too much alcohol is consumed. NMDA receptors start to become unresponsive, slowing thought in the areas of the brain they are responsible for. Contributing to this effect is the activity which alcohol induces in the gamma-aminobutyric acid system (GABA). The GABA system is known to inhibit activity in the brain. GABA could also be responsible for the memory impairment that many people experience. It has been asserted that GABA signals interfere with the registration and consolidation stages of memory formation. As the GABA system is found in the hippocampus, (among other areas in the CNS), which is thought to play a large role in memory formation, this is thought to be possible.

Blurred vision is another common symptom of drunkenness. Alcohol seems to suppress the metabolism of glucose in the brain. The occipital lobe, the part of the brain responsible for receiving visual inputs, has been found to become especially impaired, consuming 29 % less glucose than it should. With less glucose metabolism, it is thought that the cells aren't able to process images properly.

Often, after much alcohol has been consumed, it is possible to experience vertigo, the sense that the room is spinning (sometimes referred to as 'The Spins'). This is associated with abnormal eye movements called nystagmus, specifically positional alcohol nystagmus. In this case, alcohol has affected the organs responsible for balance (vestibular system), present in the ears. Balance in the body is monitored principally by two systems: the semicircular canals, and the utricle and saccule pair. Inside both of these is a flexible blob called a cupula, which moves when the body moves. This brushes against hairs in the ear, creating nerve impulses that travel through the vestibulocochlear nerve (Cranial nerve VIII) in to the brain. However, when alcohol gets in to the bloodstream it distorts the shape of the cupola, causing it to keep pressing on to the hairs. The abnormal nerve impulses tell the brain that the body is rotating, causing disorientation and making the eyes spin round to compensate. When this wears off (usually taking until the following morning) the brain has adjusted to the spinning, and interprets not spinning as spinning in the opposite direction causing further disorientation. This is often a common symptom of the hangover.[How to reference and link to summary or text]

Another classic finding of alcohol intoxication is ataxia, in its appendicular, gait, and truncal forms. Appendicular ataxia results in jerky, uncoordinated movements of the limbs, as though each muscle were working independently from the others. Truncal ataxia results in postural instability; gait instability is manifested as a disorderly, wide-based gait with inconsistent foot positioning. Ataxia is responsible for the observation that drunk people are clumsy, sway back and forth, and often fall down. It is probably due to alcohol's effect on the cerebellum.

Extreme overdoses can lead to alcohol poisoning and death due to respiratory depression.

A rare complication of acute alcohol ingestion is Wernicke encephalopathy, a disorder of thiamine metabolism. If not treated with thiamine, Wernicke encephalopathy can progress to Korsakoff psychosis, which is irreversible.

Chronic alcohol ingestion over many years can produce atrophy of the vermis, which is the part of the cerebellum responsible for coordinating gait; vermian atrophy produces the classic gait findings of alcohol intoxication even when its victim is not inebriated.

Severe drunkenness and hypoglycemia can be mistaken for each other on casual inspection, with potentially serious medical consequences for diabetics. Measurement of the serum glucose and ethanol concentrations in comatose individuals is routinely performed in the emergency department or by properly-equipped prehospital providers and easily distinguishes the two conditions.

Animal and insect modelsEdit

There have been some attempts to use animal and insect models to study the effects of ethanol on humans. Other creatures are not immune to the effects of alcohol:

Many of us have noticed that bees or yellow jackets cannot fly well after having drunk the juice of overripe fruits or berries; bears have been seen to stagger and fall down after eating fermented honey; and birds often crash or fly haphazardly while intoxicated on ethanol that occurs naturally as free-floating microorganisms convert vegetable carbohydrates to <alcohol>[17]

Birds may have even been killed by excessive consumption of alcohol.[18]

As a result, animal and insect models are fairly attractive. Heberlein et al conducted studies of fruit fly intoxication at the University of California, San Francisco in 2004.[19] The brains and nervous systems of bees bear similarities to those of humans, so honey bees are used in studies of the effect of alcohol.[20][21][22] The value of antabuse (disulfiram) as a treatment for alcoholism has been tested using a bee model.[23]

Ulrike Heberlein's group at University of California, San Francisco has used fruit flies as models of human inebriation and even identified genes that seem to be responsible for alcohol tolerance accumulation (believed to be associated with veisalgia, or hangover), and produced genetically engineered strains that do not develop alcohol tolerance[24][25][26][27]

University of Minnesota Biology Professor PZ Myers is using zebrafish to study ethanol teratogenesis and ethanol gametogenesis.[28] A wide range of other animal models have been used,[29][30] including primate,[31] mouse,[32] and rat models.[33]

See alsoEdit

ReferencesEdit

  1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11391069&query_hl=2&itool=pubmed_DocSum
  2. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Volume 44 Alcohol Drinking: Summary of Data Reported and Evaluation
  3. Garro, A.J., and Lieber, C.S. Alcohol and cancer. Annual Review of Pharmacology and Toxicology 30:219-249, 1990
  4. Blot, W.J.; McLaughlin, J.K.; Winn, D.M.; Austin, D.F.; Greenberg, R.S.; Preston-Martin, S.; Bernstein, L.; Schoenberg, J.B.; Stemhagen, A.; and Fraumeni, J.F. Smoking and drinking in relation to oral and pharyngeal cancer Cancer Research 48(11):3282-3287, 1988
  5. National Institute on Alcohol Abuse and Alcoholism Alcohol and Cancer - Alcohol Alert No. 21-1993
  6. New Scientist article "Alcohol's link to cancer explained"
  7. http://endeavor.med.nyu.edu/~strone01/doctor.html
  8. http://www.webremedies.com/quit_alcohol/know.php#5
  9. http://www.who.int/nutrition/topics/5_population_nutrient/en/index12.html
  10. http://www.who.int/nutrition/topics/5_population_nutrient/en/index13.html
  11. http://news.bbc.co.uk/2/hi/health/1780130.stm
  12. http://news.bbc.co.uk/2/hi/health/1058526.stm
  13. http://www.benbest.com/health/alcohol.html
  14. http://www.radford.edu/~kcastleb/bac.html
  15. http://apps.carleton.edu/campus/wellness/info/alcohol/bac/
  16. http://www.drugrehab.co.uk/alcohol.htm
  17. Drug Policy and Human Nature: Psychological Perspectives On The Prevention, Management, and Treatment of Illicit Drug Abuse, Warren K. Bickel, Richard J. DeGrandpre, Springer 1996 ISBN 0306452413
  18. Suspected Ethanol Toxicosis in Two Wild Cedar Waxwings, SD Fitzgerald. JM Sullivan. RJ Everson. Avian Diseases, Vol. 34, No. 2, 488-490. Apr. - Jun., 1990.
  19. http://icb.oxfordjournals.org/cgi/content/abstract/44/4/269
  20. Latest Buzz in Research: Intoxicated Honey bees may clue Scientists into Drunken Human Behavior, The Ohio State Research News, Research Communications, Columbus OH, October 23, 2004.
  21. The Development of an Ethanol Model Using Social Insects I: Behavior Studies of the Honey Bee (Apis mellifera L.): Neurobiological, Psychosocial, and Developmental Correlates of Drinking, Charles I. Abramson, Sherril M. Stone, Richard A. Ortez, Alessandra Luccardi, Kyla L. Vann, Kate D. Hanig, Justin Rice, Alcoholism: Clinical & Experimental Research. 24(8):1153-1166, August 2000.
  22. Intoxicated Honey Bees May Clue Scientists Into Drunken Human Behavior, Science Daily, October 25, 2004
  23. Development of an ethanol model using social insects: II. Effect of Antabuse on consumatory responses and learned behavior of the honey bee (Apis mellifera L.)., Abramson CI, Fellows GW, Browne BL, Lawson A, Ortiz RA., Psychol Rep. 2003 Apr;92(2):365-78.
  24. Moore, M. S., Dezazzo, J., Luk, A. Y., Tully, T., Singh, C. M., and Heberlein, U. (1998) Ethanol intoxication in Drosophila: Genetic and pharmacological evidence for regulation by the cAMP pathway. Cell 93, 997-1007
  25. Tecott, L. H. and Heberlein, U. (1998) Y do we drink? Cell 95: 733-735
  26. Bar Flies: What our insect relatives can teach us about alcohol tolerance., Ruth Williams, Naked Scientist
  27. ‘Hangover gene’ is key to alcohol tolerance, Gaia Vince, NewScientist.com news service, 22 August 2005
  28. Pharyngula blog
  29. Grant, K.A. Behavioral animal models in alcohol abuse research. Alcohol Health & Research World 14(3):187-192, 1990.
  30. Samson, H.H. Initiation of ethanol-maintained behavior: A comparison of animal models and their implication to human drinking. In: Thompson, T.; Dews, P.B.; and Barrett, J.E., eds. Neurobehavioral Pharmacology: Volume 6. Advances in Behavioral Pharmacology. Hillsdale, NJ: Lawrence Erlbaum Associates, 1987. pp. 221-248.
  31. Higley, J.D.; Hasert, M.F.; Suomi, S.J.; & Linnoila, M. Nonhuman primate model of alcohol abuse: Effects of early experience, personality, and stress on alcohol consumption. Proceedings of the National Academy of Sciences 88(16):7261-7265, 1991.
  32. Lister, R.G. The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology 92:180-185, 1987.
  33. Schwarz-Stevens, K.; Samson, H.H.; Tolliver, G.A.; Lumeng, L.; & Li, T.-K. The effects of ethanol initiation procedures on ethanol reinforced behavior in the alcohol-preferring rat. Alcoholism: Clinical and Experimental Research 15(2):277-285, 1991.

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