Naloxone and serotonin receptor subtype antagonists: interactive effects upon deprivation-induced intake

Whereas opiate receptor antagonists generally act to inhibit food intake under a variety of physiological conditions in rats, agonists of some serotonin (5-HT) receptor subtypes appear to stimulate intake, and others appear to inhibit intake. The present study evaluated the effects of the general 5-HT receptor antagonist, methysergide (1-5 mg/kg), the 5-HT2 receptor antagonists, ketanserin (1-2.5 mg/kg) and ritanserin (1-2.5 mg/kg), and the 5-HT3 receptor antagonist, ICS 205930 (1-5 mg/kg) upon deprivation (24 h)-induced intake themselves, and upon the hypophagic properties of the general opiate receptor antagonist, naloxone (1-5 mg/kg). Whereas the high doses of methysergide (0.5-4 h, 34%) and ketanserin (0.5 h, 28%) significantly decreased deprivation-induced intake themselves, ritanserin and ICS 205930 were without effect. Naloxone produced dose-dependent reductions in deprivation-induced intake (24-45%). Methysergide (1 mg/kg) significantly potentiated naloxone (5 mg/kg) hypophagia after 0.5 h. Significant potentiations of hypophagia occurred following pairing the 1 mg/kg ketanserin dose with the 1 and 5 mg/kg naloxone doses at 2 and 4 h respectively, and pairing the 2.5 mg/kg ketanserin and 1 mg/kg naloxone doses at 0.5 and 2 h. Whereas the 1 mg/kg dose of ritanserin eliminated naloxone (1 mg/kg) hypophagia over a 2-h time course, ritanserin failed to exert further effects in other dose conditions. The differences between ketanserin and ritanserin in their effects upon deprivation-induced feeding and naloxone hypophagia suggest that the former's antagonistic actions upon alpha-adrenergic receptors may be responsible for its effects.(ABSTRACT TRUNCATED AT 250 WORDS)