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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 threeminute 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.In this investigation rats' reactions to a mixture of amphetamine and amylobarbitone in a controlled environment were studied after the animals had or had not been under the influence of the same drugs while exposed to the same environment once before.Steinberg, Rushton & Tinson (1961) found that rats which were given twice-weekly trials in a simple Y-shaped runway for several weeks soon developed a relatively stable level of activity, as measured by the number of entries made into the arms of the Y in a 3-minute trial. However, when these " experienced " animals were tested after receiving drugs, they were insensitive to the stimulant effects of an amphetamine-barbiturate mixture, while " inexperienced " rats which had been similarly handled but had not been in the runway before made about three times as many entries under the influence of the drug mixture as inexperienced controls which had received saline. This showed that reactions to the drug mixture in this experimental situation were altered by the previous experience of the subjects. It had also been noted that in animals which were being tested repeatedly without drugs, activity at the second trial was usually significantly less than activity at the first trial, and this suggested that reactions to drugs also might be affected even at this early stage of familiarity with the runway. The present investigation was therefore undertaken in order to analyse the effects of first trial on second trial activity in the presence and in the absence of drugs.

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