Naloxone administration following brief exposure to novelty reduces activity and rearing in mice upon 24-h retest: a conditioned aversion?

It has recently been reported that naloxone treatment, prior to initial exposure to a novel arena, results in significant behavioural change when animals are retested 24 h later. In an attempt to clarify the nature of this delayed action of the opiate antagonist, three further studies have been performed. In the first experiment, male mice were injected with naloxone hydrochloride (0-10 mg/kg, IP) immediately after their initial experience of the test arena. When retested 24 h later, all groups that had previously received naloxone exhibited greatly reduced activity and rearing, with no evidence of a dose-response relationship. In the second experiment, naloxone (0-10 mg/kg) failed to induce a conditioned place aversion when administered according to the above regimen. In the final experiment, no evidence for a naloxone-induced taste aversion to saccharin was observed. It is concluded that the behavioural changes observed in the open-field study may reflect either (a) subtle aversive properties of naloxone which are insensitive to traditional one-trial paradigms or (b) opioid modulation of memory for non-painful experiences.