Council Park

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Rat Park is the name for a laboratory environment for housing rats , which should offer the animals as little isolation and containment as possible. It was used in the late 1970s for addiction research experiments with rats, conducted under the direction of the Canadian psychologist Bruce K. Alexander at Simon Fraser University in British Columbia , Canada.

Hypothesis - drugs do not cause addiction

Alexander's hypothesis was that the frequently observable addictive behavior in laboratory rats with access to opiates is not only due to the addictive properties of the drugs themselves, but also to the conditions in which they are kept. He told the Canadian Senate that previous experiments in which laboratory rats were kept isolated in narrow metal cages, leashed through an injection device, only indicated that "seriously desperate animals, like seriously desperate people, will pharmacologically remedy their despair if they can. "

To test this hypothesis, Alexander Rat Park built a 8.8 m² colony with 200 times the footprint of a standard laboratory cage. Sixteen to twenty rats of both sexes inhabited this colony, and there was an abundance of food, balls and wheels to play with, and enough space to mate and raise the brood. He then compared the behavior of the rats from the Rat Park colony with those who lived in a so-called Skinner box .

The results appeared to support his hypothesis : rats forced to consume morphine hydrochloride for 57 consecutive days were placed in Rat Park and given a choice between tap water and water that had been spiked with morphine. Mostly they chose the tap water. "Nothing we tried," wrote Alexander, "... produced anything like an addiction in these rats kept in a reasonably normal environment." Control groups of rats isolated in small cages consumed much more morphine in them and in the following experiments.

The disease model of drug addiction

The disease model explains addiction in terms of the effects of drugs on the reward center in the limbic system . Researchers say opiates cause changes in the mesolimbic dopaminergic system that induce feelings of pleasure. (Image: National Institute on Drug Abuse )

Some substances cause withdrawal symptoms after repeated use , which torment the user when they stop using them. What scientists disagree about is the extent to which certain substances can be said to deprive the user of self-control , not only to cause withdrawal symptoms, but also to drug addiction , which is 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. (Translation: "A behavioral pattern of drug use, characterized by extraordinary involvement in the use of a drug (compulsive use), the assurance of its availability, and a high tendency to relapse after withdrawal." Cf. drug addiction)

In the 19th century, drug addiction was seen as a sign of akrasia , lack of morality or weak will. The brain research of the 20th century replaced this moral model with a disease model of addiction , according to which addiction to a drug is a by-product of the chemical structure of the drug itself. According to the social psychologist Stanton Peele, the disease model states that tolerance, 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. (Translation: "Tolerance, withdrawal and substance craving are seen as properties of certain drugs, and the adequate use of these substances probably leaves the organism no other choice than to behave in such a stereotypical manner.") This view of drug addiction is included in the principles of the war on Drugs and slogans like heroin is so good. Don't even try it once. ("Heroin is so good. Don't try it a single time.") Or crack cocaine is instantly addictive. (" Crack is immediately addictive") reproduced.

Scientists following the disease model believe, according to Avram Goldstein, professor emeritus of pharmacology at Stanford University and leading addiction researcher, that behavior is "the business of the brain ." 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 pathway , a dopaminergic pathway that mediates feelings of will and motivation . In this pathway, heroin causes dopamine neurons to release dopamine, a neurotransmitter that creates “incentive salience” and makes the user want more. Dopamine neurons are usually inhibited by inhibitory neurons, but heroin interferes with them, so the dopamine neurons are overstimulated. The brain responds with feelings of euphoria , but the stimulation is excessive, and to protect itself from this, the brain adapts to be less sensitive to heroin.

According to the “disease model”, this has two consequences. First, it takes more heroin to get the high and at the same time makes the reward center less sensitive to the effects of the endorphins , which regulate the delivery of dopamine, so that without heroin a permanent feeling of sickness occurs. After repeated use, the user becomes tolerant and dependent, and experiences withdrawal symptoms when the heroin supply is discontinued. When the withdrawal feelings get stronger, the user loses control, writes Goldstein.

Studies in isolated laboratory mice generally confirm the disease model

The US National Institute on Drug Abuse image of a rat administering a drug to itself. Professor Avram Goldstein writes:

"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. "

“A heroin addicted rat does not rebel against society, is not a victim of socio-economic circumstances, and is not a criminal. The rat's behavior is simply controlled by the effects of heroin on its brain "

- Avram Goldstein

According to Alexander, the disease model claims one of two facts:

  • Thesis A : All or most of the people who use heroin or cocaine beyond a certain minimum amount become dependent.
  • Thesis B : Regardless of the percentage of users who become addicted to heroin and cocaine, their addiction is caused by contact with the drug.

Several decades of animal experiments were seen as supporting these theses. 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. (“If a monkey is given a lever to squeeze to inject heroin himself, he will develop a regular pattern of heroin use - a real addiction - that takes precedence over normal life activities ... As this behavior occurs in several other animal species (mainly rats) is observed, I have to conclude that if heroin were readily available to everyone, and if there were no social pressure of any kind to refrain from using heroin, a great many people would become addicted to heroin ”)

Twenty years later, Goldstein maintains the same point of view. In a document that he delivered to a methadone conference in the United States of America , 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. “Any addictive drug used by humans is also administered by rats and monkeys themselves. If we arrange so that when an animal pulls a lever it gets a shot of heroin into a vein, the animal will keep squeezing the lever until other activities (eating, sex, etc.) are excluded; it becomes addicted to heroin. A heroin addicted rat does not rebel against society, is not a victim of socio-economic circumstances, and is not a criminal. The rat's behavior is controlled simply by the effects of heroin on its brain. "

In contrast, Alexander argues that the main evidence for belief in drug-induced addiction comes from “testimony of some addicted people who believe that exposure to a drug causes them to 'lose control'” and from certain “highly technical research Laboratory animals ". He argues that this evidence has been embellished in the media to the point of being given the status of indisputable fact, whereas the bulk of historical and clinical evidence speaks against it. He writes that although opiate use was more common in the United States and England in the 19th century than it is today, the incidence of dependence and addiction never reached one percent of the population and continued to decline by the end of the century. In England heroin is still often prescribed as a drug against cough , diarrhea and chronic pain , in 1972 British doctors prescribed 29 kilograms of heroin to patients, which amounts to millions of single doses. Nonetheless, a 1982 study of iatrogenic addiction statistics in the United Kingdom found “virtual absence” of such addicts. Recent research confirms that many people who used heroin regularly for years, either for recreational or medicinal purposes, did not become addicted at all .

The Rat Park experiments

A white Wistar laboratory rat

Bruce K. Alexander's team designed a series of experiments to test the willingness of rats to consume morphine. For the Rat Park experiments they built a short tunnel, just big enough to let a rat through at a time. At the other end of the tunnel, the rats could drink a liquid from one of two dropper dispensers that automatically recorded how much each rat would drink. One dispenser contained a morphine solution, the other pure tap water .

Rats like sweet things, so in the "seduction experiment" the researchers took advantage of the rats' obvious preference for sweet things. They are investigating whether they could encourage the rats to consume morphine if the water was sweet enough. Dissolved morphine has a bitter taste for humans and appears to have the same effect on rats, wrote Alexander, for they shake their heads and refuse, as they do with bitter quinine solutions . There were four groups of rats in the seduction experiment. Group CC was isolated in laboratory cages after weaning at 22 days of age and lived there until the experiment ended at 80 days of age. Group PP was held in Rat Park for the same time . Group CP was moved from the laboratory cages to Rat Park at 65 days of age . Group PC was transferred to the cages by Council Park at the same age .

The rats in the cage (groups CC and CP) took the slightly sweetened morphine directly. In the experiments, the males in the cage took 19 times as much morphine as the males in Rat Park . No matter how much the morphine was sweetened, the rats in Rat Park usually resisted . They tried it occasionally - the females more often than the males - but they always preferred the pure water. According to Alexander it was "a significant result". It was interesting that the rats in the PC group initially refused the morphine solution, but as it got sweeter and more dilute, they started drinking as much as the rats that had lived in cages throughout the experiment. Alexander concluded that they wanted the fresh water as long as it did not interfere with normal social behavior. More significantly, when naloxone , which turns off the effects of opioids, was added to the morphine water, the rats in Rat Park started drinking it.

In another experiment, rats were forced to consume morphine in laboratory cages for 57 days and then transferred to Rat Park , where they could choose between the morphine solution and pure water. The rats now drank the pure water. They showed signs of addiction, but none 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…” (“some minor withdrawal symptoms, like twitching, yes, but there were none of these mythic seizures and sweats Sweats that you hear about so often ... ")

Alexander believes the experiments show that animal self-administration studies do not provide empirical support for the theory of drug addiction. “The strong appetite of isolated test animals for heroin and cocaine does not answer the question of how normal animals and humans react to these drugs. Ordinary people can ignore heroin. Even if it is abundant in their community and they can use these drugs with little addiction ... Rat Park rats seem to be at least as discerning. ”After a few years, Simon Fraser University ended funding for Rat Park .

Reactions to the experiment

The two major science magazines Science and Nature declined to publish the first paper by Alexander, Coambs and Hadaway, which eventually appeared in Psychopharmacology , a respectable but much smaller magazine , in 1978 . The publication of the work initially caused no reaction.

Other working groups could not replicate the results. Author Lauren Slater an interview with Herbert Kleber, director of the leading substance-abuse division of the College of Physicians and Surgeons of Columbia University ( substance abuse department of the College of Physicians and Surgeons of Columbia University ), and former drug czar of the United States on what with Rat Park runs would run ( ... on what was wrong with Rat Park ). He replied that the experiment was ingenious , but suggested that Alexander might have skewed the data in hopes of sparking public debate and that the study had methodological flaws, although he could not give examples. Slater believes Rat Park's problem was that it was being done in Vancouver , the "scientific equivalent of the tundra "

While the original experiments attracted criticism due to methodological flaws and the results were not always reproduced, the publications drew attention to the theory that the environment in which laboratory animals live may have an impact on the outcome of the addiction experiments. To date, studies from this series of experiments have been cited more than 100 times, and similar studies on the influence of living conditions on the use of other drugs have been published.

Alexander was disappointed with the public perception. But he still spoke enthusiastically of the experiments. His latest book, The Globalization of Addiction: A study in poverty of the spirit, claims that cultural uprooting stimulates all kinds of addictions, including non-drug addictions, as does isolation and drug use by laboratory animals stimulates.

Further research

Recent research has shown that improved housing conditions and environmental enrichment reduce addiction to morphine in mice. Improved environmental conditions also reduce Parkinson's disease , Huntington 's disease and Alzheimer's disease in animals .

In the last systematic review (2016) on this topic, however, it was argued that Alexander's conclusions were refuted in an experiment from 1989. The experiment concluded that rats kept in groups developed the same addiction to heroin and cocaine as when kept alone.

literature

Web links

Individual evidence

  1. ↑ a b c d e f g h Alexander K. Bruce: The Myth of Drug-Induced Addiction. 2001. Publication served on the Canadian Senate in 2001. Retrieved December 12, 2004.
  2. ↑ DE Weissman, JD Haddox: opioid pseudoaddiction: syndrome of iatrogenic. In: Pain. 36, 1989, pp. 363-366, cited in: Alexander K. Bruce: The Myth of Drug-Induced Addiction. 2001.
  3. ↑ Lauren Slater: Opening Skinner's Box: Great Psychological Experiments of the Twentieth Century. WW Norton & Company, 2004, p. 166.
  4. ↑ Drogensubstitution.at - Platform drug therapies: Information on opiate addiction - 15 years Substitutionforum Mondsee, Interdisciplinary Conference of the ÖGABS on September 9, 1999 ( Memento of the original from April 7, 2014 in the Internet Archive ) Info: The archive link was automatically inserted and not yet checked . Please check the original and archive link according to the instructions and then remove this notice. @1@ 2Template: Webachiv / IABot / www.drogensubstitution.at
  5. ↑ a b J. H. Jaffe: Drug addiction and drug abuse. In: AG Gilman, LS Goodman, TW Rall, F. Murad (Eds.): The Pharmacological Basis of Therapeutics. 7th edition. Macmillan Publishing Co., New York 1985, pp. 532-581.
  6. ^ Stanton Peele: The Meaning of Addiction. Compulsive Experience and Its Interpretation. Lexington Books, Lexington 1985, pp. 1-26. (excerpt)
  7. ↑ a b c d e Avram Goldstein: Neurobiology of Heroin Addiction and of Methadone Treatment. American Association for the Treatment of Opioid Dependence, accessed July 16, 2006.
  8. ↑ Avram Goldstein: Heroin maintenance: A medical view. A conversation between a physician and a politician. In: Journal of Drug Issues. 9, 1979, pp. 341-347.
  9. ↑ Arnold S. Trebach: The heroin solution. Yale University Press, New Haven 1982, p. 83, cited in Alexander K. Bruce: The Myth of Drug-Induced Addiction. 2001.
  10. ^ BK Alexander: The Globalization of Addiction: A study in poverty of the spirit. Oxford University Press, Oxford 2008, chap. 6th
  11. ↑ Slater 2004, p. 169.
  12. ↑ BK Alexander, RB Coambs, PF Hadaway: The effect of housing and gender on morphine self-administration in rats. In: Psychopharmacology. Vol 58, 1978, pp. 175-179. PMID 98787
  13. ↑ a b B. F. Petrie: Psychol Rep. 78, 1996, pp. 391-400. PMID 9148292
  14. ↑ MA Bozarth, A. Murray, RA Wise: Pharmacol Biochem Behav. 33 (4), Aug 1989, pp. 903-907. PMID 2616610
  15. ↑ Slater 2004, p. 171.
  16. ↑ MM Faraday, PM Scheufele, MA Rahman, NE Grunberg: Nicotine Tob Res. 1, 1999, s. 143-151. PMID 11072395
  17. ↑ Slater 2004, p. 170.
  18. ↑ Zhiwei Xu, Bing Hou, Yan Gao, Fuchu He, Chenggang Zhang: Effects of enriched environment on morphine-induced reward in mice. In: Experimental Neurology. 204, 2007, p. 714, doi: 10.1016 / j.expneurol.2006.12.027 .
  19. ↑ E. Bezard, S. Dovero, D. Belin, S. Duconger, V. Jackson-Lewis, S. Przedborski, PV Piazza, CE Gross, M. Jaber: Enriched environment confers resistance to 1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine and cocaine: involvement of dopamine transporter and trophic factors. In: The Journal of neuroscience: the official journal of the Society for Neuroscience. Volume 23, Number 35, December 2003, pp. 10999-11007. PMID 14657156 .
  20. ↑ Environmental Enrichment Lessens Protein Deficits In Mouse Model Of Huntington's. In: sciencedaily.com. March 10, 2004, accessed May 1, 2016 .
  21. ^ Memory Restored In Mice Through Enriched Environment: New Hope For Alzheimer's. In: sciencedaily.com. April 30, 2007, accessed May 1, 2016 .
  22. ↑ M. Heilig, DH Epstein, MA Nader, Y. Shaham: Time to connect: bringing social context into addiction neuroscience. In: Nature reviews. Neuroscience. Volume 17, number 9, 2016, pp. 592-599, doi: 10.1038 / nrn.2016.67 . PMID 27277868 , PMC 5523661 (free full text) (review).
  23. ↑ MA Bozarth, A. Murray, RA Wise: Influence of housing conditions on the acquisition of intravenous heroin and cocaine self-administration in rats. In: Pharmacology, biochemistry, and behavior. Volume 33, Number 4, August 1989, pp. 903-907. PMID 2616610 .