Locomotor response to novelty as a predictor of reactivity to aversive stimuli in the rat

In an animal model for vulnerability to drug abuse, animals that exhibit greater motor activity in a novel environment (high responders; HR) are more sensitive to drugs of abuse and are more likely to self-administer these drugs compared to less reactive animals (low responders; LR). In the light of clinical evidence on comorbidity between drug abuse and mood disorders, we used this model to investigate whether individual differences in locomotor reactivity to novelty are related to anxiety- and depression-like responsiveness using male Sprague-Dawley rats. Animals were categorized as HR and LR based on motor responses to novelty during a 30-min session. Anxiety-like reactivity was then measured using the elevated plus-maze, the defensive withdrawal test and acoustic startle-induced ultrasonic vocalization test. Depression-like reactivity was measured by the forced swim test. HR rats showed less anxiety-like behavior in the elevated plus-maze and defensive withdrawal tests than LR, but the opposite was true in the acoustic startle-induced vocalization test. In response to a series of loud acoustic stimuli, HR rats were faster to begin vocalizing and did so for a longer duration compared to LR. There were only minor differences between LR and HR rats in the forced swim test. These data suggest that an HR/LR model can be used to study a link between vulnerability to drug abuse and anxiety-like reactivity. The exact nature of this link depends upon the model of anxiety used and may reflect the heterogeneous nature of anxiety-like reactivity in the rat.