Neuropeptide S facilitates cue-induced relapse to cocaine seeking through activation of the hypothalamic hypocretin system.

Proc Natl Acad Sci U S A 2010 Nov 25;107(45):19567-72. Epub 2010 Oct 25.

School of Pharmacy (Pharmacology Unit), University of Camerino, 62032 Camerino, Italy.

Drug addiction is a chronic relapsing disorder characterized by compulsive drug seeking and use. Environmental conditioning factors are among the major determinants of relapse in abstinent cocaine users. Here we describe a role of the neuropeptide S (NPS) system in regulating relapse. In rats with a history of cocaine self-administration, presentation of stimuli predictive of drug availability reinstates drug seeking, triggering relapse. Intracerebroventricular (ICV) injection of NPS increased conditioned reinstatement of cocaine seeking, whereas peripheral administration of the NPS receptor antagonist SHA 68 reduced it. Manipulation of the NPS receptor system did not modify cocaine self-administration. We also found that ICV NPS administration activates c-Fos expression in hypocretin-1/orexin-A (Hcrt-1/Ox-A) immunoreactive neurons in the lateral hypothalamus (LH) and in the perifornical area (PeF). Of note, intra-LH and intra-PeF administration of NPS increased conditioned reinstatement of cocaine responding, an effect that was selectively blocked with the Hcrt-1/Ox-A receptor selective antagonist SB334867. Finally, results showed that intra-LH injection of the NPS antagonist [D-Cys(tBu) (5)]NPS blocked cue-induced cocaine seeking, indicating a role for this system in the pathophysiology of drug relapse.

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1004100107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2984152PMC
November 2010
8 Reads

Publication Analysis

Top Keywords

cocaine seeking
12
injection nps
8
cocaine self-administration
8
drug seeking
8
increased conditioned
8
conditioned reinstatement
8
nps receptor
8
administration nps
8
reinstatement cocaine
8
nps increased
8
cocaine
7
nps
7
relapse
5
seeking
5
drug
5
hcrt-1/ox-a immunoreactive
4
self-administration icv
4
immunoreactive neurons
4
modify cocaine
4
system modify
4

References

(Supplied by CrossRef)

2004

Xu et al.
The Journal of comparative neurology 2007

Endocrinology 2006

Cannella et al.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 2009

Paneda et al.
Journal of Neuroscience 2009

Ciccocioppo et al.
PNAS 2001

Harris et al.
Nature; Physical Science (London) 2005

Dayas et al.
Biological psychiatry 2008

PNAS 2005

Journal of Pharmacology and Experimental Therapeutics 2009

Ruzza et al.
2010

Similar Publications