Table 4. NOP dysregulation in depression.
These data are compiled from preclinical and clinical studies that implicate NOP and N/OFQ in behavioral constructs that relate to depression under the domains of negative valence, positive valence, and arousal/regulatory systems. CeA – central nucleus of the amygdala, SNP – single nucleotide polymorphism, N/OFQ – nociceptin/orphaninFQ, NOP – nociceptin/orphaninFQ receptor, EPM – elevated plus maze, LDB – light /dark box, FST – forced swim test, LH – learned helplessness, LPS – lipopolysaccharide, SCN – suprachiasmatic nucleus.
| Domain | Constructs | Behavioral effects | Reference |
|---|---|---|---|
| Negative Valence: | Acute threat (Fear) | Systemic or intra-CeA administration of NOP agonists decreased freezing to the conditioned stimulus | (Andero, et al., 2013; Witkin, et al., 2016) |
| G allele carriers of the rs6010719 SNP in the OPRL1 gene exhibited increased physiological startle measures of fear discrimination and greater functional connectivity between the amygdala and posterior insula. | (Andero, et al., 2013) | ||
| Potential threat (Anxiety) | N/OFQ enhanced thigmotaxis in the open field. | (Fernandez, et al., 2004) | |
| N/OFQ induced anxiogenic effects in rats on the EPM and LDB | (Fernandez, et al., 2004) | ||
| NOP agonists produced anxiolytic effects | (Duzzioni, et al., 2011) | ||
| NOP−/−mice exhibit reductions in anxiety like behavior compared to wildtype controls | (Gavioli, et al., 2007) | ||
| Sustained threat (Aversive emotional state) | NOP antagonists produce antidepressant-like effects in the FST, LH and LPS-induced depressive-like behavior | (Asth, et al., 2016; Gavioli, et al., 2003; Gavioli, et al., 2004; Goeldner, et al., 2010; Holanda, et al., 2016; Medeiros, et al., 2015) | |
| NOP−/−mice show reductions in depressive like behavior compared to their wildtype littermates. | (Gavioli, et al., 2007) | ||
| Positive Valence: | Reward Valuation | NOP agonists stimulate feeding behavior | (Ciccocioppo, et al., 2014; Nicholson, et al., 2002) |
| Arousal/Regulatory systems | Circadian rhythm | N/OFQ reduces neuronal activation in the SCN and can induce sedation | (Gompf, et al., 2005) |
| NOP ligands were more efficacious when administered during the nadir of corticosterone secretion | (Leggett, et al., 2007) |