title: Antagonism of the neuropeptide S receptor with RTI-118 decreases cocaine self-administration and cocaine-seeking behavior in rats.
abstract: Neuropeptide S (NPS) is a neuromodulatory peptide, acting via a G-protein-coupled receptor to regulate sleep, anxiety and behavioral arousal. Recent research has found that intracerebroventricular NPS can increase cocaine and alcohol self-administration in rodents, suggesting a key role in reward-related neurocircuitry. It is hypothesized that antagonism of the NPS system might represent a novel strategy for the pharmacological treatment of cocaine abuse. To this end, a small-molecule NPSR antagonist (RTI-118) was developed and tested in animal models of cocaine seeking and cocaine taking. Male Wistar rats (n=54) trained to self-administer cocaine and food under a concurrent alternating FR4 schedule exhibited specific dose-dependent decreases in cocaine intake when administered RTI-118. RTI-118 also decreased the reinstatement of extinguished cocaine-seeking behavior induced by conditioned cues, yohimbine and a priming dose of cocaine. These data support the hypothesis that antagonism of the neuropeptide S receptor may ultimately show efficacy in reducing cocaine use and relapse.
authors.affiliation: Pharmacology, Toxicology & Neuroscience, Louisiana State University Health Sciences Center, 1501 Kings Highway, Box 33932, Shreveport, LA 71130 USA. cschm1@lsuhsc.edu
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Schmoutz
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Scott P
authors.initials: SP
authors.lastname: Runyon
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Goeders
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D008297:Male; D009042:Motivation; D010080:Oxazoles / Q000494:pharmacology*; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors*; D012646:Self Administration; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D010080:Oxazoles; D011719:Pyrazines; D018013:Receptors, Neuropeptide; C568280:neuropeptide S receptor, rat; D015016:Yohimbine; D003042:Cocaine