Potency ratios of morphine and morphine-6beta-glucuronide analgesia elicited from the periaqueductal gray, locus coeruleus or rostral ventromedial medulla of rats.

The present study examined whether morphine and morphine-6beta-glucuronide (M6G) analgesia on the tail-flick and jump tests differed in potency in the periaqueductal gray, the locus coeruleus or the rostral ventromedial medulla. Morphine and M6G significantly and dose-dependently elicited analgesia on both nociceptive tests from each site. Site-specific differences were observed in the potency of M6G, but not morphine analgesia on both tests. Periaqueductal gray placements displayed analgesic ED50s on the tail-flick (morphine: 2.1 microgram, M6G: 0.2 microgram) and jump (morphine: 2.2 microgram, M6G: 0.4 microgram) tests with respective potency ratios of 12.9 and 6.5. Locus coeruleus placements displayed analgesic ED50s on the tail-flick (morphine: 1.7 microgram, M6G: 0.1 microgram) and jump (morphine: 3.4 microgram, M6G: 0.2 microgram) tests with respective potency ratios of 15.9 and 15.1. Rostral ventromedial placements displayed analgesic ED50s on the tail-flick (morphine: 1.4 microgram, M6G: 0.06 microgram) and jump (morphine: 1.9 microgram M6G: 0.08 microgram) tests with potency ratios of 21.9 on both tests. The greater analgesic sensitivity of the rostral ventromedial medulla to M6G may be due to either pharmacodynamic (splice variants of the MOR-1 gene) and/or pharmacokinetic (lipid solubility) factors.