J. COCHIN 
707 
This technique, utilizing operant-conditioning 
procedures by which the animal can control the 
frequency and to some extent the amount of drug 
it receives, has been an extremely important ad- 
vance in methodology, A cannula is inserted 
into the right atrium of the rat or monkey via 
the jugular vein and connected to a syringe 
driven through a swivel arrangement that al- 
lows free movement. An infusion pump can 
deliver a programmed series of injections auto- 
matically or it can be activated by a bar that the 
monkey presses. The animal can adjust the fre- 
quency of the lever presses until he allays his 
drug hunger or his abstinence symptoms. If the 
experimenter reduces the concentration of the 
drug and thus the amount, the animal will in- 
crease the frequency of bar presses if it is de- 
pendent. The schedules, the ratio of bar presses 
to drug infusion and the interval between re- 
wards can be adjusted as the experimenter 
wishes. There seems to be no doubt that animals 
work for morphine reward and that they will 
self administer drugs such as cocaine and am- 
phetamine where physical dependence cannot be 
an important factor.^*' The importance of these 
experiments is difficult to overestimate. There 
seems to be no doubt that the monkey closely 
resembles man in its liking for and dislike 
of drugs. The major drugs that man abuses — 
morphine, the barbiturates, cocaine amphet- 
amines, alcohol and codeine — have also been 
shown to be abused by the monkeys. 
SUMMARY 
There is no question that these procedures will 
permit investigators to study, assess and evalu- 
ate many facets of the phenomenon of addiction 
in animals which we were not able to do pre- 
viously. It is quite possible that the importance 
of evaluation of subjective drug effects will de- 
crease as such animal techniques become more 
refined and sophisticated and this is, after all, 
what animal models are for — ^to avoid doing in 
man what can be done in animals and to help us 
to understand what happens in man. 
REFERENCES 
1. Halbach, H., and Eddy, N. B. Tests for addi- 
tion (chronic intoxication) of morphine type. Bull. 
World Health Organ. 28 : 139, 1963. 
2. Collier, H. 0. J. Analgesics: Evaluation of Drug 
Activities, Pharmacometrics, Vol. 1. (D. R. Laur- 
ence and A. L. Bacharach, eds.), Academic Press, 
New York, 1964, p. 183. 
3. Winter, C. A. The physiology and pharmacology 
of pain and its relief. Analgesics (G. De Stevens, 
Ed.) , Academic Press, New York, 1965, p. 9. 
4. D'Amour, F. E., and Smith, D. L. Method for 
determining loss of pain sensation. J. Pharmacol. 
Exptl. Therap. 72:74, 1941. 
5. Grotto, M., and Sulman, F. G. Modified recep- 
tacle method for animal analgesimetry. Arch. In- 
tern. Pharmacodyn 165:152, 1967. 
6. Andrews, H. L., and Workman, W. Pain thresh- 
old measurements in dog. J. Pharmacol. Exptl. 
Therap. 73:99, 1941. 
7. Winder, C. V. Some examples of the use of statis- 
tics in pharmacology. Ann. N.Y. Acad. Sci. 
52:838, 1950. 
8. Hardy, J. D., Wolff, H. G., and Goodell, H. 
Studies on pain. New method for measuring pain 
threshold: observations on spatial summation of 
pain. J. Clin. Invest. 19:649, 1940. 
9. Eddy, N. B., and Leimbach, D. Synthetic analge- 
sics, dithienylbutenyl and dithienylbutylamines. J. 
Pharmacol. Exptl. Therap. 107:385, 1953. 
10. Cochin, J., and Kornetsky, C. Development and 
loss of tolerance to morphine in the rat after single 
and multiple injections. J. Pharmacol. Exptl. 
Therap. 145:1, 1964. 
11. Cochin, J., and Kornetsky, C. Factors in blood 
of morphine-tolerant animals that attenuate or en- 
hance effects of morphine in non-tolerant animals. 
Chapter XX. The Addictive States, Vol. XLVI. As- 
sociation for Research in Nervous and Mental Dis- 
eap°s. (Wikler, A. ed.) Williams and Wilkins Co., 
Baltimore, pp. 268-279, 1968. 
12. Haffner, F. Experimentalle prufung schmerzstel- 
lender mittel. Deut. Med. Wochschr. 55:731, 1929. 
13. Eddy, N. B. Studies of morphine, codeine and 
their derivatives; general methods. J. Pharmacol. 
Exptl. Therap. 45:339, 1932. 
14. Randall, L. 0., and Selitto, J. J. A method for 
measurement of analgesic activity on inflamed tis- 
sue. Arch. Intern. Pharmacodyn. 111:409, 1957. 
15. Siegmund, E., Cadmus, R., and Lu, G. A method 
for evaluating both non-narcotic and narcotic anal- 
gesics. Proc. Soc. Exptl. Biol. Med. 95:729, 1957. 
16. KosTER, R., Anderson, M. and De Beer, E. J. 
Acetic acid for analgesic screening. Federation 
Proc. 18:412, 1959. 
17. Emele, J. F., and Shanaman, J. Bradykinin writh- 
ing: a method for measuring analgesia. Proc. 
Soc. Exptl. Biol. Med. 114:680, 1963. 
18. EcKHARDT, E. T., Chaplovitz, F., Lifo, M. and 
Govier, W. M. Etiology of chemically induced 
writhing in mouse and rat. Proc. Soc. Exptl. Biol. 
Med. 98:186, 1958. 
19. Evans, W. O., and Bergner, D. P. A comparison 
of the analgesic potencies of morphine, pentazocine 
