Naloxone and fluid consumption in rats: dose-response relationships for 15 days

Rats were given daily intraperitoneal injections of 10.0, 1.0, 0.1, 0.01, 0.001 or 0.0 mg/kg naloxone for 15 days. Each day after the injections, animals were allowed access to a 20% sucrose solution for two hours and to tap water for the subsequent 10 hours. Consumption of the sucrose solution by the group that received 1.0 mg/kg was reliably decreased on Day 1 and 2, reflecting the suppressive effect of naloxone at that dose. By Day 3 until the end of the experiment, however, the suppression was no longer significant, suggesting that tolerance had developed. A similar effect was seen with the group given the highest dose, 10.0 mg/kg; although drinking was significantly less than the control in each of the 15 sessions, this group showed a trend to increase intake over the days of the experiment, thus also indicating possible tolerance to the effect of naloxone. Drinking patterns of the other groups did not differ statistically from the control. Thus, the low doses had no ability to suppress consumption, and the lowest dose that did lower it soon lost that ability; the highest dose continued to suppress drinking throughout the study but with decreasing efficacy. High performance liquid chromatography (HPLC) demonstrated that the naloxone remained intact over the 15 days of the experiment, supporting the suggestion that tolerance to naloxone might have developed.