AMINOGLUCOSE-INDUCED FEEDING SUPPRESSION IS REGULATED BY HYPOTHALAMICNEURONAL HISTAMINE IN RATS

Central mechanisms involved in feeding suppression produced by 1-deoxy -D-glucosamine (1-DGlcN) and 1-deoxy-N-acetylglucosamine (1-DGlcNAc) a re unclear. To clarify the mechanisms, we investigated the role of hyp othalamic neuronal histamine (HA) in feeding suppression induced by 1- DGlcN and 1-DGlcNAc in rats. Food intake was suppressed for 3 days aft er a single infusion of 24 mu mol 1-DGlcN into the third cerebroventri cle (i.c.v.). Depletion of presynaptic HA due to intraperitoneal infus ion (i.p.) of alpha-fluoromethylhistidine (FMH), a specific inhibitor of the HA synthesizing enzyme histidine decarboxylase (HDC), abolished feeding suppression completely. Blockade of postsynaptic H-1-receptor s by i.p. injection of 26 mu mol chlorpheniramine also abolished the s uppression. Oral administration of 2.4 mmol 1-DGlcNAc suppressed food intake. However, depletion of neuronal HA due to FMH did not affect th e suppression. I.c.v. infusion of 24 mu mol 1-DGlcN increased turnover rate of HA at 1 h after the infusion. Hypothalamic HA concentration, but not that of tele-methylhistamine (t-MH), increased at 24 h after i .c.v. infusion of 1-DGlcN, which suggests a correlation between HA con centration and the behavioral response. These results indicate that 1- DGlcN, but not 1-DGlcNAc, modulates feeding suppression through HA neu rons in the hypothalamus. Differences in mechanisms of feeding suppres sion by these aminoglucoses may depend on the principal sites of actio n in the brain and/or peripheral organs.