Sensitization produced by repeated administration of naloxone is blocked by food deprivation.
The current study was conducted in order to explore the effects of repeated naloxone administration as a function of food intake. Rats were trained to press a bar to avoid foot-shock. They were allowed either free or restricted access to food. Free-feeding rats developed a strong sensitivity to naloxone, as manifested by an increased shock rate after naloxone injection. When animals were food-deprived, the sensitivity was greatly reduced. A different species (mouse) and two different tests were used to examine further the effects of food intake and pretreatment with naloxone. The mice were given either free access to food or a restricted diet and were pretreated with either naloxone or saline. The effects of food intake and pretreatment with naloxone were examined in terms of motor activity, morphine analgesia and naloxone hyperalgesia. The results showed that prior exposure to naloxone in free-feeding animals enhanced the suppressant effect of naloxone on motor activity and the analgesic effects of morphine (as measured by paw-lick, but not as measured by jump in the hot-plate test), but had no effect on the hyperalgesic effect of naloxone. When mice were food-deprived during naloxone administration, sensitization did not occur. The hypothesis that naloxone sensitivity is due to changes in the number of brain opiate receptors was tested by measuring the number and affinity of [3H]naloxone binding sites on brain membranes from mice chronically treated with naloxone. Neither naloxone pretreatment nor food deprivation affected the number or affinity of binding sites. The gamma-aminobutyric acid antagonist effect of naloxone (as measured by gamma-[3H]aminobutyric acid binding) was also unchanged by naloxone pretreatment. Thus, the basis of the interactions between naloxone and the feeding state remains unclear.
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D005508:Food Deprivation / Q000502:physiology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology*; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D011957:Receptors, Opioid; D009270:Naloxone; D005680:gamma-Aminobutyric Acid; D009020:Morphine