Neuropeptide S reinstates cocaine-seeking behavior and increases locomotor activity through corticotropin-releasing factor receptor 1 in mice.

Full Abstract

Neuropeptide S (NPS) is a recently discovered neuropeptide that increases arousal and wakefulness while decreasing anxiety-like behavior. Here, we used a self-administration paradigm to demonstrate that intracerebroventricular infusion of NPS reinstates extinguished cocaine-seeking behavior in a dose-dependent manner in mice. The highest dose of NPS (0.45 nM) increased active lever pressing in the absence of cocaine to levels that were equivalent to those observed during self-administration. In addition, we examined the role of the corticotropin-releasing factor receptor 1 (CRF(1)) in this behavior as well as locomotor stimulation and anxiolysis. CRF(1) knock-out mice did not respond to either the locomotor stimulant or cocaine reinstatement effects of NPS, but still responded to its anxiolytic effect. The CRF(1) antagonist antalarmin also blocked the increase in active lever responding in the reinstatement model and the locomotor activating properties of NPS without affecting its anxiolytic actions. Our results suggest that NPS receptors may be an important target for drug abuse research and treatment and that CRF(1) mediates the cocaine-seeking and locomotor stimulant effects of NPS, but not its effects on anxiety-like behavior.

Author information

Author/s: Pañeda, Covadonga (C); Huitron-Resendiz, Salvador (S); Frago, Laura M (LM); Chowen, Julie A (JA); Picetti, Roberto (R); de Lecea, Luis (L); Roberts, Amanda J (AJ);

Affiliation: Department of Molecular and Integrative Neurosciences, The Scripps Research Institute, La Jolla, California 92037, USA. cpaneda(-atsign-)iib.uam.es

Grants: MH58543 (Agency:NIMH NIH HHS) ; NS057096 (Agency:NINDS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2009-Apr; vol 29 (issue 13) : pp 4155-61

Dates: Created 2009/04/02; Completed 2009/04/23;

PMID: 19339610, status: MEDLINE (last retrieval date: 4/23/2009, IMS Date: 23 Apr 2009 00:00:00)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Injections, Intraventricular
Mice
Mice, Inbred C57BL
Mice, Knockout
Motor Activity - drug effects; genetics; physiology
Neuropeptides - administration & dosage
Pyrimidines - pharmacology
Pyrroles - pharmacology
Receptors, Corticotropin-Releasing Hormone - antagonists & inhibitors; deficiency; metabolism
Self Administration

Associated Chemicals: CRF receptor type 1 (0) ; Dopamine Uptake Inhibitors (0) ; Neuropeptides (0) ; Pyrimidines (0) ; Pyrroles (0) ; Receptors, Corticotropin-Releasing Hormone (0) ; antalarmin (0) ; Cocaine (50-36-2)

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