THE USE OF THE ANIMAL MODEL 
IN ASSESSING ANALGESIC POTENCY 
AND DEPENDENCE LIABILITY 
J. Cochin' 
The pharmacological properties of the narcotic anal- 
gesics make it imperative to use animal screening tech- 
niques in order to assess their therapeutic usefulness 
and dangers. Animal models have been used for the as- 
sessment of the analgesic potency of the narcotic anal- 
gesics for many years, but their use for the assessment 
of dependence liability is relatively recent. Analgesic 
testing methods are usually carried out in mice or in 
rats although some have been developed for larger ani- 
mals such as the guinea pig and the dog. Dependence- 
liability, on the other hand is usually evaluated in the 
monkey, although more recently techniques have been 
worked out to assess physical and perhaps psychologi- 
cal dependence in mice and rats. Among the procedures 
used in the evaluation of analgesic potency are those 
that utilize thermal, mechanical, chemical, electrical 
and behavioral techniques. They vary from a simple re- 
flex response to a nociceptive stimulus to a complex be- 
havioral response in a complicated operant setting. 
These procedures employ apparatus that may be a little 
more than a heated wire applied to the tail or may be 
the complex electronic circuitry necessary for sophisti- 
cated operant behavioral techniques. The assessment of 
dependence liability employs methods that use refined 
observational techniques as well as procedures utilizing 
self administration of drugs. The latter may be used to 
assess both physical and psychological dependence. The 
measurement of the withdrawal syndrome in animals 
serves as an excellent model for the signs of abstinence 
in man, and the correlation of results in animals and 
man is quite good. Although most of the screening for 
such properties is done in the monkey, both the rat and 
the mouse can serve as models that have some validity. 
The induced abstinence syndrome in animals is one of a 
few disease entities in animals that parallels very closely 
that seen in man. 
INTRODUCTION 
The use of animals as models for human dis- 
ease states is a field that is fraught with diffi- 
culty both in execution and interpretation. This 
is especially true when one is concerned with 
central nervous system phenomena, where sub- 
• Boston University School of Medicine, Boston, Massachusetts. 
jective feelings, set, and observer interpretation 
of supposedly objective data play an important 
role. Thus, while the measurement of respira- 
tory depression or cardiac output might some- 
times pose enormous technical difficulties, and 
the interpretation of the meaning of the results 
may be matters of discussion and controversy, a 
reduction of tidal volume is a reduction of tidal 
volume and an increase in blood pressure is an 
increase in blood pressure. On the other hand, 
in the field of psychoactive drugs we are faced 
not only with matters of technical difficulty, 
but, in the measurement of modalities that are 
partially if not wholly subjective, we are also 
faced with the question of the interpretation of 
whatever it is we are measuring by the experi- 
mental subject or patient and the reinterpreta- 
tion of the observation by the observer or 
clinician. 
This introduction of subjective coloring of 
the measured modality has led to much chagrin, 
frustration and rationalization on the part of 
those who work with psychoactive drugs. For 
instance, the experimental production of pain 
has posed immense philosophical as well as 
practical problems. Do animals feel pain as we 
humans understand it? Are we justified in 
equating a simple reflex to a noxious stimulus 
with pain as we understand it? Obviously we 
cannot ask the animal "does it hurt?". On the 
other hand, the experimental production of pain 
in humans also poses some rather intriguing 
problems, problems that have to do with sug- 
gestibility, with the fact that the subject knows 
that he can terminate the pain at will and with 
the set, the environment and the motivation. If 
pain is a difficult assessment to make in ani- 
mals, consider the pitfalls encountered in the 
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