Delayed effects of naloxone on responsiveness to environmental novelty in rats

Two experiments were conducted to examine further the hypothesized involvement of endorphins in responsiveness to environmental novelty. In Experiment 1, rats were treated with naloxone hydrochloride (0.5–5.0 mg/kg, SC) before initial exposure to a novel arena (Day 1) and then retested in the arena 24 h later (Day 2). Only naloxone (5 mg/kg) significantly affected Day 1 performance, producing a selective reduction in locomotor activity. However, compared to saline controls, all groups that had previously received naloxone showed marked reductions in both locomotor activity and rearing upon Day 2 retest. In Experiment 2, naloxone (0.5–5.0 mg/kg) was without significant effect on performance in naive animals which had been injected on Day 1 but not exposed to the arena until Day 2. These data suggest that the delayed effects of naloxone relate specifically to the initial experience of environmental novelty rather than receptor changes or metabolite influences resulting from acute antagonist treatment. Results are discussed in relation to a possible action of naloxone upon mechanisms of attention and/or memory.