Reciprocal interactions between the amygdala and ventrolateral periaqueductal gray in mediating of Q/N_1-17-induced analgesia in the rat

The opioid peptide, Orphanin FQ/nociceptin (OFQ/N_1-17), its active fragments, and a related precursor peptide each produce analgesia following microinjection into the amygdala of rats. OFQ/N_1-17-induced analgesia elicited from the amygdala is blocked by amygdala pretreatment of either general, μ, κ, or δ-opioid antagonists even though OFQ/N_1-17 binds poorly to these receptor subtypes, and the antagonists bind poorly to the ORL-1/KOR-3 receptor. Agonists at μ and κ opioid receptors as well as β-endorphin each produce analgesia elicited from the amygdala that is blocked by opioid antagonist pretreatment in the ventrolateral periaqueductal gray (vlPAG) of rats. The present study examined whether pretreatment of general and selective opioid antagonists in the vlPAG blocked OFQ/N_1-17-induced analgesia on the tail-flick test elicited from the amygdala, and whether pretreatment of general and selective opioid antagonists in the amygdala blocked OFQ/N_1-17-induced analgesia elicited from the vlPAG of rats. OFQ/N_1-17-induced analgesia elicited from the amygdala was significantly and markedly reduced following vlPAG pretreatment with a dose range of either naltrexone, β-funaltrexamine (β-FNA, μ), nor-binaltorphamine (NBNI, κ) or naltrindole (NTI, δ). In contrast, opioid antagonists administered into misplaced mesencephalic control placements ventral and lateral to the vlPAG actually enhanced OFQ/N_1-17-induced analgesia elicited from the amygdala. OFQ/N_1-17-induced analgesia elicited from the vlPAG was significantly and markedly reduced following amygdala pretreatment with naltrexone and NBNI, to a lesser degree by NTI, and was unaffected by β-FNA. Yet, opioid antagonists administered into misplaced amygdala control placements were generally ineffective in altering OFQ/N_1-17-induced analgesia elicited from the vlPAG. Latencies were transiently increased by general, but not selective opioid antagonist treatment alone in the amygdala, but not the vlPAG. These data indicate reciprocal and regional interactions between the amygdala and vlPAG in the mediation of OFQ/N_1-17 by classic opioid receptor subtype antagonists in rats.