Behaviour in the novel environment predicts responsiveness to d-amphetamine in the rat: a multivariate approach.

The behaviour of rats in a novel environment was studied using a rapid time-sampling observation procedure followed by a principal component analysis (PCA) of the data. This approach revealed that novel environment behaviour can be described by two factors or principal components. The first factor comprised rearing, sniffing-up, ambulation and locomotion (photocell counts), and was termed "Escape". The second factor, which had high positive loadings of sniffing-down and locomotion and a high negative loading of immobility, was termed "Exploration". The scores of individual rats on the "Escape" factor predicted the stimulatory effect of acutely administered d-amphetamine (1.5mg/kg) on unconditioned behaviour. "Escape" high responders (HRs) showed more behavioural stimulation than "Escape" low responders (LRs). However, the locomotor stimulatory response of both groups increased after long-term, periodic administration of d-amphetamine and drug discrimination training, such that the level of drug-induced locomotor activity was now equivalent for the two groups. The same rats were tested twice with various doses of d-amphetamine after being trained to discriminate this drug (0.5mg/kg) from saline. "Escape" HRs were less sensitive than "Escape" LRs to the discriminative effects of 0.125-0.25mg/kg d-amphetamine. In contrast to these findings, "Exploration" HRs and LRs were not different on any of the dependent measures described above. These results are discussed in relation to the possibility that "Escape" factor scores are an indication of an animal's responsivity to novelty-induced stress. If this is the case, then animals which are more susceptible to the effects of novelty stress are more sensitive to the locomotor stimulating effects of acute d-amphetamine, but less sensitive to the cueing properties of low doses of this drug.