2-Deoxy-D-glucose antinociception and serotonin receptor subtype antagonists: test-specific effects in rats.
The antinociceptive actions of 2-deoxy-D-glucose (2-DG) are mediated in part by endogenous opioid, dopaminergic, cholinergic, histaminergic, and neurohormonal influences. Although 2-DG antinociception was not affected by tryptophan hydroxylase inhibition, a possible serotonergic role in 2-DG antinociception was investigated because of the existence of serotonin [5-hydroxytryptamine (5-HT)] receptor subtypes. The present study examined the effects of general (methysergide: 5 and 10 mg/kg), 5-HT2 (ritanserin: 2.5 mg/kg), and 5-HT3 (ICS-205,930: 0.25-5 mg/kg) receptor subtype antagonists upon 2-DG antinociception on the tail-flick and jump tests in rats. On the tail-flick test, 2-DG (450 mg/kg) antinociception was significantly reduced by all ICS-205,930 doses (48-58%) but unaffected by either methysergide (22-29% reduction) or ritanserin (6% reduction). In contrast, 2-DG antinociception on the jump test was significantly potentiated across the 120-min time course and across the 2-DG dose-response curve (100-650 mg/kg) by methysergide, ritanserin, and ICS-205,930 pretreatment. Each of the three antagonists produced significant leftward shifts in the peak and total 2-DG dose-response curve for the jump test. These data suggest different sites of action for 2-DG antinociception as a function of the pain test employed and a differential modulation by serotonin receptor subtypes at those sites.
Fisher
M C
MC
Department of Psychology and Neuropsychology Doctoral Sub-Program, Queens College, CUNY, Flushing 11367.
Bodnar
R J
RJ
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003847:Deoxyglucose / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D016713:Ritanserin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D000077526:Tropisetron
D000700:Analgesics; D007211:Indoles; D012702:Serotonin Antagonists; D016713:Ritanserin; D000077526:Tropisetron; D003847:Deoxyglucose