Neuropeptide FF exerts pro- and anti-opioid actions in the parabrachial nucleus to modulate food intake

Neurons that synthesize the morphine modulatory peptide neuropeptide FF (NPFF; Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2) densely innervate the parabrachial nucleus (PBN), an area implicated in regulating food intake. We analyzed opioid-related actions of NPFF in feeding in adult male Sprague-Dawley rats. Unilateral infusion of 2 nmol/0.5 µl of the µ-opioid receptor agonist [D-Ala2,NMe-Phe4,glycinol5]enkephalin (DAMGO) into the lateral PBN increased 4-h food intake from 0.7 ± 0.1 to 3.3 ± 0.3 g. NPFF (1.25-5.0 nmol) prevented this hyperphagic µ-opioidergic action. In rats fed after 4-h deprivation (baseline = 12.3 ± 0.3 g/2 h), 5 nmol of NPFF did not alter and larger doses (10 and 20 nmol) actually increased food intake (+36, 54%). Twenty nanomoles also elevated intake of freely feeding rats (from 0.7 ± 0.1 to 5.1 ± 1.0 g/4 h). The opioid receptor blocker naloxone (10 nmol) antagonized this increase. These data reveal both pro- and anti-opioid actions of NPFF in the PBN to modulate feeding. The mechanisms for the opposite actions of low and high concentrations of this neuropeptide in parabrachial regulation of food intake remain to be determined.