Differential actions of central alloxan upon opioid and nonopioid antinociception in rats.
Spontaneous or induced diabetes, as well as glucose loading, reduce opiate antinociception, presumably through induction of hyperglycemia. While peripheral administration of alloxan is a potent pancreatic beta-cell toxin, intracerebroventricular (ICV) alloxan reduces glucoprivic feeding in the absence of hyperglycemia, presumably through interactions with specific brain glucoreceptors. Our laboratory demonstrated that opioid-mediated 2-deoxy-D-glucose (2DG) antinociception is significantly reduced by central pretreatment with alloxan, and that this deficit is reversed by coadministration with 3M-D-glucose. The present study compared ICV and intravenous (IV) routes of alloxan (200 micrograms) upon morphine (1-10 mg/kg, SC) analgesia on the tail-flick and jump tests in rats, and evaluated these effects in terms of concomitant changes induced by ICV alloxan upon nonopioid-mediated continuous cold-water swim (CCWS: 2 degrees C for 3.5 min) antinociception. Two weeks following central, but not peripheral pretreatment with alloxan, morphine (2.5 and 5.0 mg/kg, SC) antinociception was markedly (30-56%) reduced on both nociceptive tests. In contrast, central pretreatment with alloxan respectively reduced (30 min) and subsequently potentiated (60 and 90 min) CCWS antinociception on the jump test. Alterations in antinociception by central alloxan occurred in the absence of changes in basal nociceptive thresholds, hypothermia or hyperglycemia. These data suggest that central alloxan may be acting upon either specific, but unidentified brain glucoreceptors and/or a glucoprivic control mechanism.
Lubin
E
E
Department of Psychology, Queens College, CUNY, Flushing 11367.
Bodnar
R J
RJ
D000496:Alloxan / Q000008:administration & dosage*; D000698:Analgesia; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains
D000700:Analgesics; D000496:Alloxan; D009020:Morphine