MadSci Network: Neuroscience

Re: what experiments can be done to test if chocolate is addictive?

Date: Fri Feb 11 01:21:44 2000
Posted By: Kevin Caldwell, Faculty, Neurosciences, University of New Mexico
Area of science: Neuroscience
ID: 949459869.Ns

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 

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, 

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 

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?
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.

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 

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 

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:,2283,1467,00.html

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