A potential role of saline trials in morphine-induced place-preference conditioning.

The necessary conditions to alter rats' initial preferences for two sides of a shuttlebox were investigated, using procedures that are often used in the study of drug reinforcement. In Experiment 1, pairings of morphine sulfate (15 mg/kg, intraperitoneally) and either the nonpreferred side or a holding box was factorially combined with alternate-day pairings of saline and either the preferred side or a holding box. Pairings of saline and the preferred side were necessary and sufficient to increase preferences for the initially nonpreferred side. In Experiment 2, pairings of saline and the nonpreferred side, but not the holding box, strengthened the initial preference, regardless of whether morphine or saline injections preceded alternate-day holding-box placements. In Experiment 3, injection and placement in the preferred side in an unpaired manner, or placement only, decreased preferences for that side more than saline injections alone or no treatment. Paired saline injections and placement produced a greater change in preference than no treatment.