Effects of the putative 5-HT1A receptor antagonist NAN-190 on free feeding and on feeding induced by the 5-HT1A receptor agonist 8-OH-DPAT in the rat.

The effects of the putative 5-HT1A receptor antagonist NAN-190 on feeding and spontaneous locomotor activity in rats were examined. The drug elicited a robust, dose-dependent (0.01-10 mg/kg) increase in food consumption in free feeding animals. Microstructural analysis of feeding induced by NAN-190 (3 mg/kg) revealed that the drug increased the duration of feeding and number of feeding bouts but decreased the feeding rate. The increase in feeding induced by 3 mg/kg of NAN-190 was not apparent until 2-4 h after injection. This prolonged latency to onset of the feeding response appeared to be due to response competition. Thus, a 'neuroleptic-like' action of the drug on spontaneous motor activity was observed during the the initial 2 h following injection. A dopamine receptor antagonist action of NAN-190 was also indicated by the results of studies in which the drug was observed to block oral stereotypy induced by the dopamine receptor agonist apomorphine. In interaction studies, NAN-190 (0.1 and 10 mg/kg) failed to block the feeding response induced by the prototypical 5-HT1A receptor agonist 8-OH-DPAT (0.0625 and 1.0 mg/kg) and indeed, appeared to have an additive effect with 8-OH-DPAT on consummatory behaviour. These data suggest that NAN-190 may act as a partial agonist rather than an antagonist at the 5-HT1A receptor and also provide the first evidence that the drug has dopamine receptor antagonist properties in vivo.