Strain differences in response to escapable and inescapable novel environments and their ability to predict amphetamine-induced locomotor activity

Rationale. Locomotor response to novelty predicts locomotor and reinforcing effects of psychostimulant drugs in outbred rats. Among Lewis and Fischer 344 (F344) inbred rats this association is less clear, perhaps due to strain-selective differences in responses to novelty. Objective. We examined responses to novel inescapable and escapable environments and to novel objects in these strains. Methods. Experiment 1 utilized a place conditioning procedure. Rats were confined to one side for 8 days and then allowed access to both this (familiar) and the novel sides. Experiment 2 assessed locomotor response within an inescapable environment. On another occasion, contacts with novel objects within a novel environment were tabulated. Corticosterone levels and fecal boli were measured. Whether these responses predicted amphetamine-induced locomotor activity was determined. To further assess genetic contributions to this association, experiment 3 assessed novelty responses in F1 hybrid Lewis-F344 rats. Results. Lewis rats showed greater novelty-seeking behavior in the escapable environment but lower locomotor activity in the inescapable environment compared to F344 rats. There were no strain differences in novel object contacts, corticosterone, or fecal boli responses. Baseline corticosterone levels and activity levels in the novel environment were positively correlated with amphetamine activity based on data from all rats. However, novelty and amphetamine-induced activity showed non-significant negative correlations in F344 and Lewis rats. Yet, F1 rats showed a significant positive correlation between these variables, even though some of their other responses were Lewis-like or F344-like. Conclusions. These data suggest that responses to different novelty situations are strain-dependent. Electronic Publication