Opioid antagonists in the periaqueductal gray inhibit morphine and beta-endorphin analgesia elicited from the amygdala of rats.

In addition to brainstem sites of action, analgesia can be elicited following amygdala microinjections of morphine and mu-selective opioid agonists. The present study examined whether opioid analgesia elicited by either morphine or beta-endorphin in the amygdala could be altered by either the general opioid antagonist, naltrexone, the mu-selective antagonist, beta-funaltrexamine (BFNA) or the delta 2 antagonist, naltrindole isothiocyanate (Ntii) in the periaqueductal gray (PAG). Both morphine (2.5-5 micrograms) and beta-endorphin (2.5-5 micrograms) microinjected into either the baso-lateral or central nuclei of the amygdala significantly increased tail-flick latencies and jump thresholds in rats. The increases were far more pronounced on the jump test than on the tail-flick test. Placements dorsal and medial to the amygdala were ineffective. Naltrexone (1-5 micrograms) in the PAG significantly reduced both morphine (tail-flick: 70-75%; jump: 60-81%) and beta-endorphin (tail-flick: 100%; jump: 93%) analgesia elicited from the amygdala, indicating that an opioid synapse in the PAG was integral for the full expression of analgesia elicited from the amygdala by both agonists. Both BFNA (68%) and Ntii (100%) in the PAG significantly reduced morphine, but not beta-endorphin analgesia in the amygdala on the tail-flick test. Ntii in the PAG was more effective in reducing morphine (60%) and beta-endorphin (79%) analgesia in the amygdala on the jump test than BFNA (15-24%). Opioid agonist-induced analgesia in the amygdala was unaffected by opioid antagonists administered into control misplacements in the lateral mesencephalon, and the small hyperalgesia elicited by opioid antagonists in the PAG could not account for the reductions in opioid agonist effects in the amygdala. These data indicate that PAG delta 2, and to a lesser degree, mu opioid receptors are necessary for the full expression of morphine and beta-endorphin analgesia elicited from the amygdala.