Quantitative Measurement of the Effect of Lysergic Acid Diethylamide on Mice and its Interactions with other Drugs

Abstract

ALTHOUGH several species of animals (including spiders, fighting fish, pigeons and rats) have been used for the quantitative evaluation of the effect of hallucinogenic and psychotomimetic agents it is worth while to add to this list owing to the biochemical differences between species. The present favourite seems to be the rat¹. This communication reports a test for the quantitative evaluation of the effect of psychotomimetic agents using mice chosen for their small size (useful if limited quantities of agent—for example, extracts from schizophrenic serum—are available) and ease of handling. A Latin square design was used employing four cages, each of 5 mice, and four modes of injection (saline, lysergic acid diethylamide, drug to be tested, and lysergic acid diethylamide and this drug together). The mice were injected subcutaneously and placed individually on the centre of a vertical pole at 1 min. intervals. The time (up to a maximum of 40 sec.) taken by the mice to reach lines drawn 1 in. from the top or bottom of the pole was then measured. Variability can be reduced by eliminating slow or erratic mice in preliminary tests. (The mice can also be trained to run down the pole under hunger drive. This procedure, however, introduces two new parameters—learning and hunger—which may be differentially affected by drugs.) Doses of lysergic acid diethylamide of 1 and 2 mgm./kgm. were used. The solutions were always freshly prepared and the effect tested of their interaction with adrenochrome, adrenolutin and the brom derivative of lysergic acid diethylamide. Fig. 1 shows the difference between the drug value and its matching saline value, with the latter corrected to a straight line at the level of the first saline value (maximum possible score = 200). All statistical work was done, however, on uncorrected results. As the results obtained were not normally distributed, all statistical evaluations were carried out using non-parametric methods (Wilcoxon's method for paired data).