|MadSci Network: Neuroscience|
For a detailed discussion of the use of laboratory animals to determine whether a substance is likely to be abused and cause addiction in humans, I suggest that you refer to the following: 1 "Animal Models of Drug Addiction", which appears in the book Psychopharmacology: The Fourth Generation of Progress, edited by Floyd E. Bloom and David J. Kupfer, Raven Press, Ltd., New York, 1995. This is an excellent overview of drug abuse research methods written by Dr. George Koob, a leading authority in this research area from The Scripps Research Institute. 2 "Drug Reinforcement in Animals", written by Marilyn E. Carroll and Adande J. Mattox, in Drug Addiction and its Treatment: Nexus of Neuroscience and Behavior, edited by Bankole A. Johnson and John D. Roache, Lippincott-Raven Publishers, Philadelphia, 1997. 3 "Prediction of Drug Abuse Liability from Animal Studies", written by Tomoji Yanagita, in Methods of Assessing the Reinforcing Properties of Abused Drugs, edited by Michael A. Bozarth, Springer-Verlag, New York, 1987 The following brief discussion was written, primarily, using information in these three references. First, you need to know what it means for a substance to be addictive. Dr. Koob states at the start of his chapter, "Two characteristics are common to definitions of dependence and addiction: a compulsion to take the drug with a loss of control in limiting intake and a withdrawal syndrome that results in physical as well as motivational signs of discomfort when the drug is removed. The concept of reinforcement or motivation is a crucial part of both of these characteristics." He also states that, "Most models and definitions of drug dependence also involve the development of tolerance and dependence, which appear to onset and decay with a similar time course." Second, you need to question whether it is appropriate to perform your studies using an animal model, rather than humans. In general, the answer is yes. Drs. Carroll and Mattox astutely state, "The use of animal models that mimic the different phases of addiction has been essential to the development and evaluation of behavioral, pharmacologic, and social interventions for drug abuse." Drugs which are abused by humans (e.g., psychomotor stimulants, ethanol, nicotine, opiates, barbiturates and benzodiazepines) have strong reinforcing effects in laboratory animals, as evidenced by the fact that the animals will perform many different, and often relatively complex and repetitive, tasks to obtain the drugs. However, there is variability across mammals in their abuse of certain drugs. This variability results from pharmacokinetic (absorption, distribution and metabolism and excretion) differences and brain sensitivity differences; the latter of these is dependent on brain neurochemistry, which, in turn, is dependent on the genetic make-up of the animal. Now, what types of procedures are employed to determine whether a substance is addictive? 1. DRUG SELF-ADMINISTRATION The basic question being asked in these procedures is can an animal learn to perform a certain task, such as press a lever, in order to gain access to a drug? Often, the drug is administered intravenously, although oral administration may be employed. For example, studies on ethanol abuse commonly administer the drug orally. Yanagita states, "Generally speaking, the intravenous route is more reinforcing than the oral route, probably because of the sharper rise and higher peak value of the blood level, as well as the shorter duration of the CNS effects, which may make it easier for the animal to discriminate the drug effects and lead to more frequent responding on the lever." The abuse liability of a drug can be determined by comparing the complexity of the task that the animal will perform in order to receive the drug to how hard it will "work" to get a prototypic drug (i.e., one that is known to be addictive). The complexity is altered by changing the schedule (e.g., fixed-ratio, second-order, multiple) of reinforcement. 2. BRAIN STIMULATION REWARD Koob states, "Electrical self-stimulation of certain brain areas is rewarding for animals and humans as demonstrated by the fact that subjects will readily self-administer the stimulation……Intracranial self-stimulation differs significantly from drug self-administration in that, in this procedure, the animal is working to directly stimulate presumed reinforcement circuits in the brain and the effects of drugs are assessed on these reward thresholds. Drugs of abuse decrease thresholds for ICSS [intracranial self-stimulation], and there is a good correlation between the ability of drugs to decrease ICSS thresholds and their abuse potential." 3. PLACE PREFERENCE In this procedure the animal is exposed to two or more neutral environments: in a simplified version of this procedure, an animal is exposed to two neutral environments- for example, the two arms of a T-shaped box. These environments are then paired with different drug states (for example, receiving an injection of cocaine compared to an injection of caffeine; or an injection of cocaine compared to an injection of a placebo). Later, the animal is allowed access to both environments and the amount of time spent in each is considered a measure of the reinforcing value of the drug (or placebo) that the animal receives in that environment. That is, the greater the positive reinforcing properties of a drug, the more time that an animal will spend in that side of the chamber. In your case, you could compare chocolate and caffeine or chocolate and sugar- but, note, that you need to consider the influence of taste on your results. 4. DRUG DISCRIMINATION This procedure is used to determine whether a drug produces subjective effects that are similar to or are different from a second drug. For example, you can question whether the subjective effects of cocaine are similar to those of amphetamine. Or, in your case, are the subjective effects of chocolate similar to those of caffeine? Dr. Koob describes this procedure as, "Drug discrimination typically involves training an animal to produce a particular response in a given drug state for a food reinforcer and to produce a different response in the placebo or drug-free state…….The choice of response that follows administration of an unknown [or, known] test compound can provide valuable information about the similarity of that drug's interoceptive cue properties to those of the training drug." I hope that this information is of assistance to you. Finally, when I searched the internet for information about chocolate addiction, I found these sites: http://www.hhp.ufl.edu/fit/article/choc.htm
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