Rat Park

Rat Park was a study into drug addiction conducted in the 1970s by Canadian psychologist Bruce K. Alexander at Simon Fraser University in British Columbia, Canada.

Alexander's hypothesis was that drugs do not cause addiction, and that the apparent addiction to morphine commonly observed in laboratory rats exposed to it is attributable to their living conditions, and not to any addictive property of the drug itself. Alexander, Bruce K., (2001) [http://www.parl.gc.ca/37/1/parlbus/commbus/senate/com-e/ille-e/presentation-e/alexender-e.htm "The Myth of Drug-Induced Addiction"] , a paper delivered to the Canadian Senate, January 2001, retrieved December 12, 2004.] He told the Canadian Senate in 2001 that experiments in which laboratory rats are kept isolated in cramped metal cages, tethered to self-injection apparatus, show only that "severely distressed animals, like severely distressed people, will relieve their distress pharmacologically if they can." [Weissman, D. E. & Haddox, J. D. (1989). "Opioid pseudoaddiction: an iatrogenic syndrome," "Pain", 36, 363-366, cited in Alexander 2001, "op cit".]

To test his hypothesis, Alexander built Rat Park, a 200-square-foot (18.6 m²) housing colony, 200 times the square footage of a standard laboratory cage. There were 16–20 rats of both sexes in residence, an abundance of food, balls and wheels for play, and private places for mating and giving birth. Slater, Lauren. (2004) "Opening Skinner's Box: Great Psychological Experiments of the Twentieth Century", W.W. Norton & Company, p. 166.] The results of the experiment appeared to support his hypothesis. Rats who had been forced to consume morphine hydrochloride for 57 consecutive days were brought to Rat Park and given a choice between plain tap water and water laced with morphine. For the most part, they chose the plain water. "Nothing that we tried," Alexander wrote, "... produced anything that looked like addiction in rats that were housed in a reasonably normal environment."

The two major science journals, "Science" and "Nature", rejected Alexander's paper, which appeared instead in "Pharmacology, Biochemistry and Behavior", a respectable but much smaller journal, and the paper's publication attracted no response. Alexander, B.K., Beyerstein, B.L., Hadaway, P.F., and Coambs, R.B. "Effect of early and later colony housing on oral ingestion of morphine in rats," "Pharmacology Biochemistry and Behavior", Vol 15, 4:571-576. PMID 7291261] Because of the lukewarm reception, Simon Fraser University withdrew Rat Park's funding.

The disease model of drug addiction

left|thumb|240px|The_disease_model_explains_addiction_with_reference_to_the_action_of_drugs_on_the_reward pathways in the limbic system. Researchers say that opiates cause changes in the mesolimbic dopaminergic pathway that produce feelings of pleasure. (Image courtesy of the National Institute on Drug Abuse.)It is not disputed that some substances cause withdrawal symptoms after repeated use, leaving the user dependent on the substance to prevent the withdrawal. Where scientists differ is over the extent to which certain substances can be said to rob the user of self control, causing not only a dependence — defined solely by what's called the "abstinence syndrome", or withdrawal Jaffe, J.H. Drug addiction and drug abuse. In: Gilman, A.G.; Goodman, L.S.; Rall, T.W.; Murad, F. (eds), The Pharmacological Basis of Therapeutics (7th edition), p 532-581. New York: Macmillan Publishing Co., 1985.] — but a drug addiction, defined as "a behavioral pattern of drug use, characterized by overwhelming involvement with the use of a drug (compulsive use), the securing of its supply, and a high tendency to relapse after withdrawal."

In the 19th century, drug addiction was regarded as a sign of akrasia, or weakness of the will. Late 20th century brain research appeared to invalidate this psychosocial model and replaced it with a disease model, according to which addiction to a drug is a by-product of the chemical structure of the drug itself. According to social psychologist Stanton Peele, the disease model states that " [t] olerance, withdrawal, and craving are thought to be properties of particular drugs, and sufficient use of these substances is believed to give the organism no choice but to behave in these stereotypical ways." Peele, Stanton. "The Meaning of Addiction. Compulsive Experience and Its Interpretation". Lexington: Lexington Books, 1985, pp. 1-26. [http://www.peele.net/lib/moa1.html excerpt] ] This view of drug addiction is reflected in the policies of the War on Drugs and in slogans such as "Heroin is so good. Don't even try it once," or "Crack cocaine is instantly addictive."

Scientists adhering to the disease model believe that behavior is "the business of the brain," according to Avram Goldstein, Professor Emeritus of Pharmacology at Stanford University, and a leading researcher into drug addiction. Goldstein writes that the site of action of heroin and all other addictive drugs is a bundle of neurons deep in the brain called the mesolimbic dopaminergic pathway, a reward pathway that mediates feelings of pleasure. Within this pathway, heroin causes dopamine neurons to release dopamine, the pleasure hormone. Dopamine neurons are normally held in check by inhibitory neurons, but heroin shuts these down, allowing the dopamine neurons to become overstimulated. The brain responds with feelings of euphoria, but the stimulation is excessive, and in order to protect itself against this, the brain adapts by becoming less sensitive to the heroin. Goldstein, Avram. [http://www.aatod.org/1998-3.html "Neurobiology of Heroin Addiction and of Methadone Treatment"] , American Association for the Treatment of Opioid Dependence, retrieved July 16, 2006.]

This has two consequences, according to the disease model. First, more heroin is required to produce the high, and at the same time, the reward pathway becomes less sensitive to the effects of endorphins, which regulate the release of dopamine, so that without heroin, there is a persistent feeling of sickness. After repeated intake, the user becomes tolerant and dependent, and undergoes withdrawal symptoms if the heroin supply is terminated. As the feelings of withdrawal worsen, the user loses control, writes Goldstein, and becomes an addict.

Most animal studies support the disease model

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right|thumb|280px|Image_from_the_U.S._National_Institute_on_Drug_Abuse_of_a_rat_self-administering_a_drug._Professor_Avram_Goldstein_writes:_heroin is not rebelling against society, is not a victim of socioeconomic circumstances, is not a product of a dysfunctional family, and is not a criminal. The rat's behavior is simply controlled by the action of heroin (actually morphine, to which heroin is converted in the body) on its brain." ]

According to Alexander, the disease model makes two claims:

*Claim A: All or most people who use heroin or cocaine beyond a certain minimum amount become addicted.
*Claim B: No matter what proportion of the users of heroin and cocaine become addicted, their addiction is caused by exposure to the drug.

Several decades of animal studies have consistently supported these claims. Avram Goldstein wrote in 1979: "If a monkey is provided with a lever, which he can press to self-inject heroin, he establishes a regular pattern of heroin use — a true addiction — that takes priority over the normal activities of his life ... Since this behavior is seen in several other animal species (primarily rats), I have to infer that if heroin were easily available to everyone, and if there were no social pressure of any kind to discourage heroin use, a very large number of people would become heroin addicts. Goldstein, Avram. "Heroin maintenance: A medical view. A conversation between a physician and a politician," "Journal of Drug Issues", 9, 341-347, 1979.]

Twenty years later, Goldstein maintains the same position. In a paper delivered to a 1997 U.S. methadone conference, he wrote: "Every addictive drug used by people is also self-administered by rats and monkeys. If we arrange matters so that when an animal presses a lever, it gets a shot of heroin into a vein, that animal will press the lever repeatedly, to the exclusion of other activities (food, sex, etc.); it will become a heroin addict. A rat addicted to heroin is not rebelling against society, is not a victim of socioeconomic circumstances, is not a product of a dysfunctional family, and is not a criminal. The rat's behavior is simply controlled by the action of heroin (actually morphine, to which heroin is converted in the body) on its brain."

Against this, Alexander argues that the only evidence for the belief in drug-induced addiction comes from "the testimonials of some addicted people who believe that exposure to a drug caused them to 'lose control'," and from some "highly technical research on laboratory animals". He argues that this evidence has been embellished in the news media to the point where it has acquired the status of an unassailable fact, whereas the great bulk of empirical evidence, he says, runs against it. He writes that, although the use of opiates in the United States and England during the 19th century was greater than it is now, the incidence of dependence and addiction never reached one percent of the population and was declining at the end of the century. In Britain, he writes that heroin has been widely used in medication for coughs, diarrhea, and chronic pain until the present day; in 1972, British doctors prescribed 29 kilograms of heroin to patients, which he writes amounts to millions of doses, yet a 1982 study of the statistics on iatrogenic addiction in the UK showed a "virtual absence" of such addicts. [Trebach, Arnold S. "The Heroin solution", New Haven: Yale University Press, 1982, p. 83, cited in Alexander 2001 "op cit".]

The Rat Park experiments

In Rat Park, Alexander built a short tunnel large enough to accommodate one rat at a time. At the far end of the tunnel, the rats could drink a fluid from one of two drop dispensers, which automatically recorded how much each rat drank. One dispenser contained a morphine solution and the other plain tap water.

Alexander designed a number of experiments to test the rats' willingness to consume the morphine. Rats have a sweet tooth, so in an experiment called "The Seduction," the researchers exploited the rats' apparent sweet tooth to test whether they could be enticed to consume morphine if the water was sweet enough. Morphine in solution has a bitter taste for humans, and appears to have the same effect on rats, Alexander writes, since they shake their heads and reject it as they do with bitter quinine solutions. The Seduction involved four groups of rats. Group CC was isolated in laboratory cages when they were weaned at 22 days of age, and lived there until the experiment ended at 80 days of age; Group PP was housed in Rat Park for the same period; Group CP was moved from laboratory cages to Rat Park at 65 days of age; and Group PC was moved out of Rat Park and into cages at 65 days of age.

The caged rats (Groups CC and PC) took to the morphine instantly, even with virtually no sweetener, with the caged males drinking 19 times more morphine than the Rat Park males. But no matter how sweet the morphine became, the rats in Rat Park resisted it. They would try it occasionally — with the females trying it more often than the males — but invariably they showed a preference for the plain water. It was, writes Alexander, "a statistically significant finding." He writes that the most interesting group was Group CP, the rats who were brought up in cages but moved to Rat Park before the experiment began. These animals rejected the morphine solution when it was stronger, but as it became sweeter and more dilute, they began to drink almost as much as the rats that had lived in cages throughout the experiment. They wanted the sweet water, he concluded, so long as it did not disrupt their normal social behavior. Even more significant, he writes, was that when he added a drug called Naloxone, which negates the effects of opioids, to the morphine-laced water, the Rat Park rats began to drink it.

In another experiment, he forced rats in ordinary lab cages to consume morphine for 57 days on end, giving them no liquid to drink other than the morphine-laced solution, then moved them into Rat Park, where he allowed them to choose between the morphine solution and plain water. They drank the plain water. He writes that they did show some signs of dependence, but no sign of addiction. There were "some minor withdrawal signs, twitching, what have you, but there were none of the mythic seizures and sweats you so often hear about ..." Slater 2004, p. 169.]

Alexander believes his experiments show that animal self-administration studies provide no empirical support for the theory of drug-induced addiction, and that the theory has no other basis in empirical science, although it has not been disproven. "The intense appetite of isolated experimental animals for heroin and cocaine in self-injection experiments tells us nothing about the responsiveness of normal animals and people to these drugs. Normal people can ignore heroin ... even when it is plentiful in their environment, and they can use these drugs with little likelihood of addiction ... Rats from Rat Park seem to be no less discriminating."

Reaction to the experiment

The two major science journals "Science" and "Nature" rejected Alexander's paper, which was published in "Pharmacology, Biochemistry and Behavior", a much smaller publication. Because of the study's poor reception, Simon Fraser University withdrew its funding.

Some later studies did appear to confirm its findings — for example, Bozarth, Murray and Wise in 1989, also published in "Pharmacology, Biochemistry and Behavior" — but nothing came of those either. Writer Lauren Slater interviewed psychiatrist Herbert Kleber, director of the substance-abuse division of the College of Physicians and Surgeons of Columbia University, and a former U.S. deputy drug czar, on what was wrong with Rat Park. He replied that the experiment was "ingenious," but suggested that Alexander may have distorted the data in the hope of provoking a public debate, and that the study had methodological flaws, though he did not state examples. Slater believes Rat Park's problem was that it was conducted in Vancouver, the "scholarly equivalent of the tundra." Slater 2004, p. 171.]

While the original experiment attracted criticism for methodological flaws and its results could not be exactly reproduced, Petrie, B.F., Psychol Rep. 1996, 78, 391-400. PMID 9148292] the publications did draw attention to the idea that the environment that laboratory animals live in might influence the outcome in experiments related to addiction. As of 2006, papers from the series of experiments have been cited more than 100 times, and similar studies on the influence of living conditions on the consumption of other drugs have been published. M.M. Faraday, P.M. Scheufele, M.A. Rahman, N.E. Grunberg, Nicotine Tob Res. 1999, 1, 143-51, PMID 11072395]

Alexander was disappointed by the reception, and still speaks of the experiments enthusiastically. "We talked about it all the time, over dinner, on weekends. My kids came up and met the rats, did some data collection. It was of course tremendously exciting to see all the commonly held notions about addiction so challenged by the rats. I've had only one good idea in my life and that was it. But one good idea, who can complain about that?" Slater 2004, p. 170.]

Related research

Recent research has shown that an enriched environment may decrease morphine addiction in mice [http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WFG-4MXBFC5-1&_user=1510518&_coverDate=04%2F30%2F2007&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000053381&_version=1&_urlVersion=0&_userid=1510518&md5=4ef66824a4078f1d77000d9b0b262074] . Enriched environments also decrease deficits in animal models of Parkinson's disease, [http://www.jneurosci.org/cgi/content/full/23/35/10999] Huntington's disease, [http://www.sciencedaily.com/releases/2004/03/040309072325.htm] and Alzheimer's disease. [http://www.sciencedaily.com/releases/2007/04/070429154909.htm]

Notes

References

*Alexander, Bruce K., (2001) [http://www.parl.gc.ca/37/1/parlbus/commbus/senate/com-e/ille-e/presentation-e/alexender-e.htm "The Myth of Drug-Induced Addiction"] , a paper delivered to the Canadian Senate, January 2001, retrieved December 12, 2004.
*Alexander, Bruce K. [http://www.policyalternatives.ca/index.cfm?act=news&do=Article&call=224&pA=BB736455&type=2,3,4,5,6,7 "The Roots of Addiction in Free Market Society"] , Canadian Centre for Policy Alternatives, April 2001
*Bozarth, M.A., Murray, A. & Wise, R.A. (1989) "Influence of housing conditions on the acquisition of intraveneous heroine and cocaine self-administration in rats, "Pharmacology, Biochemistry, and Behavior", 33, 903-907.
*Davies, J.B. (1992) [http://www.psychedelic-library.org/davies/myth_of_addiction.htm "The Myth of Addiction: An application of the psychological theory of attribution to illicit drug use,"] Harwood Academic Publishers, Char, Switzerland
*Goldstein, Avram. (1979) "Heroin maintenance: A medical view. A conversation between a physician and a politician," "Journal of Drug Issues", 9, 341-347.
*Goldstein, Avram. (1997) [http://www.aatod.org/1998-3.html Neurobiology of Heroin Addiction and Methadone Treatment] , a paper written for the 1997 American Association for the Treatment of Opioid Dependence methadone conference, retrieved December 12, 2004.
*Goldstein, Avram. [http://www.aatod.org/1998-3.html "Neurobiology of Heroin Addiction and of Methadone Treatment"] , American Association for the Treatment of Opioid Dependence, retrieved July 16, 2006.
*Jaffe, J.H. "Drug addiction and drug abuse," in Gilman, A.G.; Goodman, L.S.; Rall, T.W.; Murad, F. (eds), "The Pharmacological Basis of Therapeutics" (7th edition), p 532-581. New York: Macmillan Publishing Co., 1985.]
*Jones, J. B. (1999) [http://www.netowne.com/historical/tennessee/drugs.htm "The Use and Abuse of Drugs in Nineteenth-Century Tennessee History] , retrieved December 12, 2004
*Peele, Stanton. "The Meaning of Addiction: Compulsive Experience and its Interpretation", Lexington Books, Lexington, 1985, [http://www.peele.net/lib/moa1.html excerpt] retrieved December 12, 2004
*Slater, Lauren. (2004) "Opening Skinner's Box: Great Psychological Experiments of the Twentieth Century", W.W. Norton & Company, ISBN 0-393-05095-5
*Trebach, Arnold S. The Heroin solution, New Haven: Yale University Press, 1982.
*Weissman, D. E. & Haddox, J. D. (1989). "Opioid pseudoaddiction: an iatrogenic syndrome," Pain, 36, 363-366.
* [http://www.nida.nih.gov/ Website of the U.S. National Institute on Drug Abuse]
* [http://www.drugsense.org/wodclock.htm Website of Drug Sense]
* [http://www.aatod.org/ Website of the American Association for the Treatment of Opioid Dependence]

Further reading

*Alexander, B.K., Beyerstein, B.L., Hadaway, P.F., and Coambs, R.B. (1981) "Effect of early and later colony housing on oral ingestion of morphine in rats," "Pharmacology Biochemistry and Behavior", Vol 15, 4:571-576. PMID 7291261
*Alexander, B.K. (1985) "Drug use, dependence, and addiction at a British Columbia university: Good news and bad news," "Canadian Journal of Higher Education", 15, 77-91.
*Alexander, B.K. (1987) "The disease and adaptive models of addiction: A framework evaluation," "Journal of Drug Issues" 17, pp. 47-66.
*Alexander, B.K. (1990) "Peaceful measures: Canada's way out of the War on Drugs", Toronto University Press. ISBN 0-8020-6753-0
*Alexander, B.K. (2000) "The globalization of addiction," "Addiction Research"
*Drucker, E. (1998) "Drug Prohibition and Public Health," U.S. Public Health Service, Vol. 114
*Goldstein, A. "Molecular and Cellular Aspects of the Drug Addictions". Springer-Verlag, 1990. ISBN 0-387-96827-X
*Goldstein, A."From Biology to Drug Policy", Oxford University Press, 2001. ISBN 0-19-514664-6
* [http://www.whitehousedrugpolicy.gov/publications/policy/03budget/index.html Website of the U.S. Office of National Drug Control Policy]
*Peele, Stanton. [http://web.archive.org/web/20040707104659/http://surreal.tripod.com/drugaddiction.htm A discussion about addiction] , archived link from July 7, 2004.