Naltrexone, serotonin receptor subtype antagonists, and glucoprivic intake: 1. 2-Deoxy-D-glucose

Inhibition of deprivation-induced intake by naloxone was significantly enhanced by the 5-hydroxytryptamine3 (5-HT3) antagonist ICS-205,930. Interactions between naloxone and either the general 5-HT antagonist methysergide or the 5-HT2 antagonist ritanserin or ketanserin produced smaller effects. The present study evaluated whether 2-deoxy-D-glucose (2DG, 400 mg/kg) hyperphagia was affected by methysergide (0.5-5 mg/kg), ritanserin (0.25-2.5 mg/kg), or ICS-205,930 (0.5-5 mg/kg) alone or in combination with naltrexone (0.25 and 2.5 mg/kg). Only ICS-205,930 stimulated spontaneous intake for up to 4 h in the light cycle. Only ritanserin (1.25 mg/kg) transiently reduced 2DG hyperphagia. The dose-dependent decreases in 2DG hyperphagia by naltrexone were significantly enhanced by the dose range of ICS-205,930. The inhibition of 2DG hyperphagia by the low naltrexone dose was enhanced by methysergide (5 mg/kg) and ritanserin (1.25 mg/kg). These data suggest that the 5-HT3 receptor primarily interacts with opioid systems to modulate 2DG hyperphagia and that one possible locus of interaction is in the caudal brainstem.