Differential effects of the 5-HT 1B/2C receptor agonist mCPP and the 5-HT1A agonist flesinoxan on hypothalamic neuropeptide Y in the rat: evidence that NPY may mediate serotonin's effects on food intake.

To determine whether NPY and 5-HT interact, we studied the effects on hypothalamic NPY and NPY mRNA levels of acute (10 mg/kg) and 7-day administration (10 mg/kg/day) of mCPP (a 5-HT 1B/2C agonist) and flesinoxan (a 5-HT 1A agonist). After both treatments, mCPP reduced food intake and NPY levels in the PVN (p < 0.01). NPY mRNA levels were only increased by comparable food restriction (p < 0.05). Acute flesinoxan injection increased food intake and NPY levels in the PVN and ARC (p < 0.01). This suggests that food intake changes induced by mCPP and flesinoxan are associated with altered NPYergic activity. Stimulation of different hypothalamic 5-HT1 receptors may alter NPY levels available for release in the PVN, possibly by altering transport along the ARC-PVN projection. Therefore, inhibition of the ARC-PVN projection may at least partly mediate the hypophagic effects of serotonin.