Effects of methadone on free feeding in satiated rats

A variety of opioids and opiates are known to increase short-term food intake. In the present study, we evaluated the effects of methadone on free feeding in satiated rats. We assessed the effect of methadone (0, 1.5, 3.0, 5.0, and 10.0 mg/kg) on food intake 1, 2, 4, and 6 h after injection for 3 consecutive days. Two hours after methadone administration, food intake was inversely related to dose, but after 6 h a direct relationship between dose and feeding was obtained. Food intake increased with repeated methadone administration. In Experiment 2, methadone (5.0 mg/kg) was injected and food was made available 0, 1, 2, or 3 h later. Maximal food intake occurred in the third and fourth hours following methadone administration. As in Experiment 1, food intake increased with repeated methadone administration. Increases in food intake following repeated methadone administration may have been due to the development of tolerance to effects of methadone that may interfere with feeding, such as sedation. In Experiment 3, methadone was administered daily or every fifth day, assuming that spacing injections would retard tolerance development. Repeated daily methadone administration was associated with increased food intake earlier in the session, whereas increases in food intake following spaced methadone administration occurred later in the session. These data indicate that methadone increases short-term feeding in satiated rats. This is in contrast to the reported decrease in food-reinforced behavior noted in operant studies. This contrast may be due to sedating or other disabling effects of methadone.