Differential actions of central alloxan upon opioid and nonopioid antinociception in rats: A further examination

Previous work demonstrated that central pretreatment with alloxan significantly reduced antinociception induced by morphine and 2-deoxy-D-glucose (2DG), an opioid-mediated stressor, but not induced by continuous cold-water swims (CCWS), a nonopioid-mediated stressor. The alloxan-induced deficits in 2DG antinociception were ameliorated by coadministration of D-glucose (3 M, 3M-DG). The present study evaluated this relationship further by: 1. a) examining whether central alloxan reduced morphine antinociception following either simultaneous 3M-DG and alloxan coadministration, alloxan followed 10 days later by 3M-DG and 3M-DG alone, and 2. b) determining whether central alloxan pretreatment altered nonopioid antinociception induced by the muscarinic cholinergic agonist, pilocarpine. Morphine (2.5-5 mg/kg, SC) antinociception on the tail-flick and jump tests was significantly reduced by central alloxan. In contrast, simultaneous coadministration of 3M-DG and alloxan failed to alter morphine antinociception. This ameliorative effect of 3M-DG was not due to its ability to affect morphine antinociception, and was time-dependent in that delays in 3M-DG administration failed to affect the alloxan-induced deficit. Central alloxan pretreatment failed to alter pilocarpine antinociception on the tail-flick test, and increased pilocarpine antinociception on the jump test. That central alloxan reduced opioid (e.g., morphine and 2DG), but not nonopioid (e.g., CCWS, pilocarpine) forms of antinociception suggests a specific mode of action, possibly through disruptions of glucoprivic control mechanisms which is in keeping with the suggestion that opioid systems are sensitive to changes in central glucose function.