Journal
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
Volume 103, Issue 2, Pages 332-337Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbb.2012.09.003
Keywords
Cocaine; Neuropeptide S; Self-administration; Relapse; Reinstatement; Yohimbine
Funding
- National Institutes of Health from the National Institutes of Mental Health [1R01MH087826]
- Department of Pharmacology, Toxicology Neuroscience
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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. (C) 2012 Elsevier Inc. All rights reserved.
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