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.
Williams
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Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Dourish
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CT
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D004435:Eating / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013239:Stereotyped Behavior / Q000187:drug effects
D010879:Piperazines; D011954:Receptors, Dopamine; D012702:Serotonin Antagonists; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D001058:Apomorphine