Paradoxical response to the sedative effects of diazepam and alcohol in C57BL/6J mice lacking the neuropeptide S receptor.

Abstract:

:The neuropeptide S (NPS) system is characterized by a unique pharmacology because it has anxiolytic-like effects and promotes arousal and wakefulness. To shed light on this peptidergic system, we tested the sedative effect of the central depressants diazepam and ethanol on the loss of righting reflex in mice lacking the neuropeptide S receptor (NPSR), NPSR(-/-). Furthermore, we tested the effect of the intracerebroventricular (ICV) administration of NPS on the sedative effect of diazepam and ethanol in NPSR(-/-) and their wild type counterpart NPSR(+/+). Finally, we evaluated the effect of the pro-arousal neuropeptides CRF and Hcrt-1/Ox-A in NPSR-deficient mice. Contrary to our expectations, the results showed that the NPSR(-/-) were less sensitive to the hypnotic effects of both diazepam and ethanol compared with their wild type littermates. ICV NPS was able to attenuate the sedative effect of both alcohol and diazepam in wild type mice, but not in the NPSR(-/-) line. The administration of CRF and Hcrt-1/Ox-A, two classic pro-arousal peptides, elicited the same effects in both NPSR(-/-) and wild type mice, ruling out the possibility that adaptive mechanisms occurring at the level of these two systems could have occurred during NPSR(-/-) development to compensate for the lack of NPSR receptors. Our findings demonstrated that the deletion of NPSR leads to minor changes in the arousal behavior of mice. Moreover, we demonstrated that the deletion of NPSR did not lead to compensatory changes in the vigilance-promoting effects of the CRF and Hcrt-1/Ox-A systems.

journal_name

Peptides

journal_title

Peptides

authors

Ghazal P,Corsi M,Roth A,Faggioni F,Corti C,Merlo Pick E,Pucciarelli S,Ciccocioppo R,Ubaldi M

doi

10.1016/j.peptides.2014.09.010

subject

Has Abstract

pub_date

2014-11-01 00:00:00

pages

107-13

eissn

0196-9781

issn

1873-5169

pii

S0196-9781(14)00278-2

journal_volume

61

pub_type

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