Effects of a single experience on subsequent reactions to drugs

The activity of rats in an unfamiliar environment was studied in order to determine how far their reactions to an amphetamine-barbiturate mixture depended on whether or not they had been under the influence of this mixture while exposed to the same environment once before. The environment consisted of a Y-shaped runway, and the activity studied was the number of entries into the arms of the Y during a three-minute trial; the two trials took place three days apart. At the first trial the drug mixture practically doubled activity. At the second trial rats which had been under the influence of the drug mixture at the first trial were again made more active by the drug mixture, but the drug mixture did not increase the activity of rats which had received only saline at the first trial. These results showed that a single brief exposure to an unfamiliar environment can markedly affect subsequent reactions to drugs, and interactions of this kind may have to be taken into account when it is desired to use animals repeatedly in tests of the action of drugs on behaviour. The drug mixture also produced ataxia which was assessed quantitatively by measuring the variability of the "splay" of the rats' footprints; ataxia was unaffected by previous experience.