Relevance of drug discrimination methods for the evaluation of antipsychotic drugs

Neuropeptide Y (NPY) has been shown to mimic the effects of some σ receptor agonists in the brain and to possess the same proabsorptive effect as these agonists in the isolated mouse jejunum. The aim of the present study was to investigate the effect of NPY on duodenal alkaline secretion in the rat and to define its mode of action. NPY (0.01 to 3 ωg/kg i.v.) induced a dose-related increase in duodenal bicarbonate secretion, the maximal effect being obtained at 1 ωg/kg. This response was significantly inhibited by the i.v. administration of haloperidol, BMY 14802, devazepide, hexamethonium, tetrodotoxin and by bilateral truncal vagotomy, but not by SCH 23390, sulpiride, prazosin or atropine, whereas i.c.v. devazepide had no effect. This pharmacological profile is identical to that reported for σ receptor agonists. The results suggest that NPY and σ ligands act through a common pathway to stimulate duodenal alkaline secretion in the rat.