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The University of Minnesota runs a number of studies involving non-human primates, most notably research into drug addiction. The studies have attracted the attention of local and national animal rights groups, most especially the drug addiction studies of Marilyn Carroll, which she performs on primates, rats, and mice.
Non-human primates are used by the university to research the effects of drug addiction. The studies are led by Marilyn Carroll, a professor of psychiatry and neuroscience. [1] As of October 2000, Carroll's laboratory was using 34 rhesus monkeys in these studies, according to a meeting of the university's Social Concerns Committee, [2] a figure confirmed in a May 15, 2006 census obtained by the Minnesota Primate Freedom Project, a chapter of the national Primate Freedom Project. [3] Carroll has received $8,888,593 in grants for her work from the National Institutes of Health (NIH) since 1996. [4]
Carroll's research involves training monkeys and rats — for example by restricting food intake [5] — to self-administer drugs that humans misuse. In the experiments, the animals drink alcohol, smoke, and are given cocaine, heroin, caffeine, nicotine, and alcohol intravenously (only rats self-administer intravenously). [6] She writes that "several phases of the addiction process are modeled, such as acquisition, maintenance, withdrawal, craving, and relapse." [1]
Her work has shown that antidepressants and behavioral or environmental changes, such as adding sweet-tasting drinking solutions, reduce the self-administration of drugs in laboratory animals. [1] Other changes, such as limiting food intake, led to increased drug administration. [7]
Carroll's work has also demonstrated that primates will become upset and mutilate themselves when forced to smoke cocaine; she notes in a publication: "Monkey M-V became very agitated and excitable when smoking cocaine. M-V’s state became more severe and incidents of self-mutilatory behavior occurred, specifically biting the upper leg area [...] One monkey showed considerable aggressive, self-mutilatory behavior during this time, throwing itself against the sides and top of its cage. As a result, it developed sinusitis and skin infections. [8]
Carroll's work on primates and other species has gained the attention of animal rights groups, including the Animal Liberation Front (ALF). [9] Protests were first held outside her lab in 1986. [10] Pictures of animal experiments were later sent to 400 of her neighbors, and her home was picketed. [6] [10] In 1997, Freeman Wicklund of the university's Student Organization for Animal Rights (SOAR) was sentenced to 90 days in jail after occupying the office of the president of the university to protest Carroll's research. Wicklund responded by beginning a hunger strike, which he told reporters would last until he was released; he was released two weeks later and given a year's probation instead. [9] Carroll obtained a restraining order against SOAR, the ALF, and several of the protesters, including Wicklund. [11] In 1998, Wicklund denounced the ALF, his previous activism, and made a proclamation of embracing pacifism; this move largely caused the campaign against Marilyn Carroll's research to deflate. [12]
The city in which she lives (Mahtomedi, MN) has since passed an ordinance attempting to prevent activists from picketing at her home. [13]
Along with these national groups, Carroll's work has been the continued focus of local groups via on-campus protests, banner hangs, and other methods of campus messaging. Organizations working on this issue include Progress for Science [14] and the Animal Rights Coalition "No Pain in My Name" campaign. [15]
Harry Frederick Harlow was an American psychologist best known for his maternal-separation, dependency needs, and social isolation experiments on rhesus monkeys, which manifested the importance of caregiving and companionship to social and cognitive development. He conducted most of his research at the University of Wisconsin–Madison, where humanistic psychologist Abraham Maslow worked with him for a short period of time.
Rat Park was a series of studies into drug addiction conducted in the late 1970s and published between 1978 and 1981 by Canadian psychologist Bruce K. Alexander and his colleagues at Simon Fraser University in British Columbia, Canada.
Dizocilpine (INN), also known as MK-801, is an uncompetitive antagonist of the N-Methyl-D-aspartate (NMDA) receptor, a glutamate receptor, discovered by a team at Merck in 1982. Glutamate is the brain's primary excitatory neurotransmitter. The channel is normally blocked with a magnesium ion and requires depolarization of the neuron to remove the magnesium and allow the glutamate to open the channel, causing an influx of calcium, which then leads to subsequent depolarization. Dizocilpine binds inside the ion channel of the receptor at several of PCP's binding sites thus preventing the flow of ions, including calcium (Ca2+), through the channel. Dizocilpine blocks NMDA receptors in a use- and voltage-dependent manner, since the channel must open for the drug to bind inside it. The drug acts as a potent anti-convulsant and probably has dissociative anesthetic properties, but it is not used clinically for this purpose because of the discovery of brain lesions, called Olney's lesions (see below), in laboratory rats. Dizocilpine is also associated with a number of negative side effects, including cognitive disruption and psychotic-spectrum reactions. It inhibits the induction of long term potentiation and has been found to impair the acquisition of difficult, but not easy, learning tasks in rats and primates. Because of these effects of dizocilpine, the NMDA receptor pore-blocker ketamine is used instead as a dissociative anesthetic in human medical procedures. While ketamine may also trigger temporary psychosis in certain individuals, its short half-life and lower potency make it a much safer clinical option. However, dizocilpine is the most frequently used uncompetitive NMDA receptor antagonist in animal models to mimic psychosis for experimental purposes.
The Emory National Primate Research Center located in Atlanta, Georgia, owned by Emory University, is a center of biomedical and behavioral research, is dedicated to improving human and animal health, and is the oldest of seven National Primate Research Centers partially funded by the National Institutes of Health. It is known for its nationally and internationally recognized biomedical and behavioral studies with nonhuman primates by Emory University.
In internal medicine, relapse or recidivism is a recurrence of a past condition. For example, multiple sclerosis and malaria often exhibit peaks of activity and sometimes very long periods of dormancy, followed by relapse or recrudescence.
(–)-2-β-Carbomethoxy-3-β-(4-fluorophenyl)tropane is a stimulant drug used in scientific research. CFT is a phenyltropane based dopamine reuptake inhibitor and is structurally derived from cocaine. It is around 3-10x more potent than cocaine and lasts around 7 times longer based on animal studies. While the naphthalenedisulfonate salt is the most commonly used form in scientific research due to its high solubility in water, the free base and hydrochloride salts are known compounds and can also be produced. The tartrate is another salt form that is reported.
Experiments involving non-human primates (NHPs) include toxicity testing for medical and non-medical substances; studies of infectious disease, such as HIV and hepatitis; neurological studies; behavior and cognition; reproduction; genetics; and xenotransplantation. Around 65,000 NHPs are used every year in the United States, and around 7,000 across the European Union. Most are purpose-bred, while some are caught in the wild.
Phenyltropanes (PTs) were originally developed to reduce cocaine addiction and dependency. In general these compounds act as inhibitors of the plasmalemmal monoamine reuptake transporters. Although RTI holds a strong position in this field, they are not the only researchers that have prepared these analogues. This research has spanned beyond the last couple decades, and has picked up its pace in recent times, creating numerous phenyltropanes as research into cocaine analogues garners interest to treat addiction.
Naphthylaminopropane (PAL-287) is an experimental drug under investigation as of 2007 for the treatment of alcohol and stimulant addiction.
Joseph Vincent Brady was an American psychologist, neuroscientist, and pioneer of behavioral pharmacology. In addition to his status as a founder of behavioral pharmacology, he made significant contributions in the areas of drug abuse and treatment, space exploration, and human research ethics.
RTI(-4229)-150, is a phenyltropane derivative which acts as a potent dopamine reuptake inhibitor and stimulant drug. It is around 5x more potent than cocaine, but is more selective for the dopamine transporter relative to the other monoamine transporters. RTI-150 has a fast onset of effects and short duration of action, and its abuse potential in animal studies is similar to that of cocaine itself; its main application in scientific research has been in studies investigating the influence of pharmacokinetics on the abuse potential of stimulant drugs, with the rapid entry of RTI-150 into the brain thought to be a key factor in producing its high propensity for development of dependence in animals. RTI-150 is not explicitly illegal anywhere in the world, but its similar structure and pharmacological activity to cocaine makes it possible that it would be considered a controlled substance analogue in countries such as the USA, Canada, Australia and New Zealand which have controlled substance analogue legislation.
RTI(-4229)-336, is a phenyltropane derivative which acts as a potent and selective dopamine reuptake inhibitor and stimulant drug. It binds to the dopamine transporter with around 20x the affinity of cocaine, however it produces relatively mild stimulant effects, with a slow onset and long duration of action. These characteristics make it a potential candidate for treatment of cocaine addiction, as a possible substitute drug analogous to how methadone is used for treating heroin abuse. RTI-336 fully substitutes for cocaine in addicted monkeys and supports self-administration, and significantly reduces rates of cocaine use, especially when combined with SSRIs, and research is ongoing to determine whether it could be a viable substitute drug in human cocaine addicts.
Self-administration is, in its medical sense, the process of a subject administering a pharmacological substance to themself. A clinical example of this is the subcutaneous "self-injection" of insulin by a diabetic patient.
RTI(-4229)-113 is a stimulant drug which acts as a potent and fully selective dopamine reuptake inhibitor (DRI). It has been suggested as a possible substitute drug for the treatment of cocaine addiction. "RTI-113 has properties that make it an ideal medication for cocaine abusers, such as an equivalent efficacy, a higher potency, and a longer duration of action as compared to cocaine." Replacing the methyl ester in RTI-31 with a phenyl ester makes the resultant RTI-113 fully DAT specific. RTI-113 is a particularly relevant phenyltropane cocaine analog that has been tested on squirrel monkeys. RTI-113 has also been tested against cocaine in self-administration studies for DAT occupancy by PET on awake rhesus monkeys. The efficacy of cocaine analogs to elicit self-administration is closely related to the rate at which they are administered. Slower onset of action analogs are less likely to function as positive reinforcers than analogues that have a faster rate of onset.
RTI(-4229)-112 is a synthetic stimulant drug from the phenyltropane family. In contrast to RTI-113, which is DAT selective, RTI-112 is a nonselective triple reuptake inhibitor.
RTI(-4229)-177 is a synthetic stimulant drug from the phenyltropane family, which acts as a DRI with micromolar affinity for the SERT. RTI-177 has an unusually long duration of action of 20 hours or more, substantially longer than the related compound RTI-336 from which it differs in molecular structure only by the absence of a p-methyl group.
7-OH-DPAT is a synthetic compound that acts as a dopamine receptor agonist with reasonable selectivity for the D3 receptor subtype, and low affinity for serotonin receptors, unlike its structural isomer 8-OH-DPAT. 7-OH-DPAT is self-administered in several animal models, and is used to study addiction to cocaine.
SKF-77,434 is a drug which acts as a selective dopamine D1 receptor partial agonist, and has stimulant and anorectic effects. Unlike other D1 agonists with higher efficacy such as SKF-81,297 and 6-Br-APB, SKF-77,434 does not maintain self-administration in animal studies, and so has been researched as a potential treatment for cocaine addiction.
Marian Rita Weinbaum Fischman was an American psychologist. She researched narcotics and addiction.
James David Jentsch is an American neuroscientist. He is the Empire Innovation Professor of Psychology at Binghamton University. His research considers the neurobiological origins of psychoses and addiction. Jentsch was awarded the 2011 AAAS Award for Scientific Freedom and Responsibility.
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