Blockade of nociceptin/orphanin FQ receptor signaling reverses LPS-induced depressive-like behavior in mice

tNociceptin/orphanin FQ is the natural ligand of a Gi-protein coupled receptor named NOP. This peptider-gic system is involved in the regulation of mood states and inflammatory responses. The present studyaimed to investigate the consequences of blocking NOP signaling in lipopolysaccharide (LPS)-inducedsickness and depressive-like behaviors in mice. LPS 0.8 mg/kg, ip, significantly induced sickness signssuch as weight loss, decrease of water and food intake and depressive-like behavior in the tail suspensiontest. Nortriptyline (ip, 60 min prior the test) reversed the LPS-induced depressive states. The NOP receptorantagonist SB-612111, 30 min prior LPS, did not modify LPS-induced sickness signs and depressive-likebehavior. However, when injected 24 h after LPS, NOP antagonists (UFP-101, icv, and SB-612111, ip) sig-nificantly reversed the mood effects of LPS. LPS evoked similar sickness signs and significantly increasedtumor necrosis factor- (TNF-) and interleukin-6 (IL-6) plasma levels 6 h post-injection in wild-type((NOP(+/+)) and NOP knockout ((NOP(−/−)) mice. However, LPS treatment elicited depressive-like effectsin NOP(+/+) but not in NOP(−/−) mice. In conclusion, the pharmacological and genetic blockade of NOPsignaling does not affect LPS evoked sickness signs while reversing depressive-like behavior.