Morphine-induced stereotyped thigmotaxis could appear as enhanced fear and anxiety in some behavioural tests

This study questions whether the classical interpretation for unconditional fear/anxiety tests is valid when animals are under the influence of some drugs of abuse. We used a modified version of the trimethylthiazoline (TMT)—avoidance task, a measure of unconditional fear. Halfway into a corridor maze we placed a 3-cm-high barrier. This provided a wall in the middle of the corridor, one that the mice can easily climb over. Saline- and morphine-treated mice were randomly placed in the ‘safe’ or ‘unsafe’ (TMT) side and observed for 10 min. As expected, saline-injected mice spent only about 25% of the time in the TMT side, regardless of the side they were initially placed into. In contrast, morphine-treated mice did not cross the barrier even once, regardless of their initial placement. Specifically, morphine-treated mice initially placed in the TMT side appeared to exhibit the expected reduction in unconditional fear, that is, spending the entire time in the TMT side, a significant increase over the controls. Yet, morphine-treated mice placed in the safe side never even entered the TMT side; thus, these mice appeared to exhibit a behavioural response that is classically interpreted as increased fear, that is, spending significantly less time in the TMT side versus the controls. In summary, this study demonstrates that the classical interpretation of some unconditioned fear or anxiety tests could be misleading when animals are under the influence of drugs that might induce other competing behaviours.