A Rat Test for Drug Addiction. ∗

Abstract

Further experiments on the addiction liability of various drugs in the albino rat have been carried out by the method previously described. 1 The test measures objectively progressive changes in the degree of irritability of the animal 24 hours after withdrawal of the drug throughout the period of administration. Advantage is thus taken of the most outstanding part of the abstinence syndrome clinically and experimentally, hyperirritability, to assess the ability of a drug to produce addiction.

The irritability of the rat which is normally fairly constant for a series of animals is quantitatively measured by determining the struggle response to a uniformly uncomfortable situation. Such a situation is provided by lashing the animal in the supine position to a small animal board so constructed that the animal is free to struggle but can neither injure nor extricate itself. Graphic records of each struggle are made kymographically by a light lever attached to the skin overlying the xyphoid process. The response of the animal is expressed by the number of struggles per interval and is a quantitative index of the degree of irritability of the animal at that time.

Daily administration of morphine, codeine, or heroine results consistently in progressive increase of 24-hour abstinence hyper-irritability as shown by the struggle response to the above described uniformly uncomfortable situation. 1 Control animals receiving injections of water showed only a gradual decrease in irritability under the same experimental conditions.

Dihydromorphinone hydrochloride (dilaudid): To completely eliminate the movements of rats in the device described above, dilaudid was 10 times as potent as morphine. Complete tranquilization was obtained with dilaudid in one-tenth of the dosage necessary with morphine. When daily doses of equal tranquilizing potency were given, no significant difference in addiction liability could be found between dilaudid and morphine.