CENTRAL EFFECTS OF NEUROPEPTIDE FF ON INTESTINAL MOTILITY IN NAIVE AND MORPHINE-DEPENDENT RATS

The effects on intestinal myoelectric activity of (1DME)Y8Fa (D-Tyr-D-Leu[N-Me]-Phe-Gln-Pro-Gln-Arg-Phe-NH2), a synthetic analog of the neuropeptide FF (Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2) were examined in rats after central (i.c.v.) administration performed before acute morphine and after chronic morphine treatment. The acute administration of morphine sulphate (5 mg/kg s.c.) inhibited the occurrence of intestinal migrating myoelectric complexes (MMC) for 46.0 +/- 15.2 min and increased the number of contractions on the proximal colon (13.5 +/- 2.9 vs 8.1 +/- 0.6/10 min). The duration of the MMC disruption was significantly (P < 0.05) reduced (19.0 +/- 5.6 min) by central administration of naloxone (100 mu g/kg) but not of (1DME)Y8Fa. In rats rendered tolerant to morphine by injections of a slow-release emulsion containing morphine (75 mg/rat over 48 h), intestinal MMC were disrupted and replaced by a continuous irregular activity. Central administration of naloxone (100 mu g/kg) restored MMC after having induced for 38.3 +/- 7.3 min a motor pattern typical of the diarrhoeal state, termed minute rhythm. No change in colonic motility was observed despite the occurrence of dirrahoea. The effects of naloxone were reproduced by (1DME)Y8Fa (100 mu g/kg) that induced a pattern of minute rhythm for 48.9 +/- 15.7 min. These features indicate that neuropeptide FF has no action on the acute effects of morphine on intestinal motility but exerts anti-opioid activities in digestive motor alterations associated to morphine withdrawal.