Acute and subchronic treatments with selective serotonin reuptake inhibitors increase Nociceptin/Orphanin FQ (NOP) receptor density in the rat dorsal raphe nucleus; interactions between nociceptin/NOP system and serotonin

Role of nociceptin/orphanin FQ and nociceptin opioid peptide receptor in depression and antidepressant effects of nociceptin opioid peptide receptor antagonists

“…In line with in vitro studies, an in vivo microdialysis study shows that N/OFQ infusion into the DR decreases extracellular levels of 5-HT in rats, which is significantly attenuated by prior infusion of [Nphe 1 ]NC(1–13)NH 2 , NOP receptor antagonist, into DR [80]. In contrast to these studies, N/OFQ infusion into the DR increases extracellular 5-HT, an effect that is blocked by concomitant infusion of UFP-101, while UFP-101 alone is devoid of any intrinsic effect [81]. Although the reason for this discrepancy is not clear, it seems likely that N/OFQ may exert biphasic effect on 5-HT neurons in the DR: low doses of N/OFQ (1–10 µM) stimulate 5-HT neurons via NOP receptor on GABA neurons through disinhibition [81], but high doses of N/OFQ (100–300 µM) suppress 5-HT neurons in the DR [80] (Fig.…”

“…4). In addition, several in vitro [7879] and in vivo [81] studies using UFP-101 suggests that there is no tonic inhibition of endogenous N/OFQ on 5-HT release in the DR. However, there is a contradictory report that local infusion of [Nphe 1 ]NC(1–13)NH 2 alone into the DR increases 5-HT release in the DR, suggesting a tonic inhibition of endogenous N/OFQ on 5-HT release in the DR [80].…”