Endotoxin- and interleukin-1-induced hypophagia are not affected by adrenergic, dopaminergic, histaminergic, or muscarinic antagonists

Endotoxin (lipopolysaccharide, LPS) and interleukin-1 (IL-1) administration induce hypophagia in rodents. Both IL-1 and LPS are known to activate cere bral norepinephrine and serotonin metabolism, and IL-1 affects that of acet ylcholine and histamine. Each of these neurotransmitters has been implicate d in feeding behavior. Therefore, the ability of specific antagonists of th e above neurotransmitter systems to counteract feeding responses to periphe rally injected mIL-1 beta and LPS was studied. Feeding was assessed in nond eprived mice by measuring the intake of sweetened milk in a 30-min period, as well as daily food pellet intake. LPS and mIL-1 beta reliably reduced mi lk intake, and often reduced food pellet intake and body weight. Treatment of the mice with peripherally administered alpha-adrenergic (phentolamine o r prazosin) or beta-adrenergic antagonists (propranolol), either alone or i n combination, did not significantly alter the hypophagic responses to mIL- 1 beta or LPS. Mice in which cerebral norepinephrine was depleted with DSP- 4 or 6-hydroxydopamine also displayed the usual hypophagia in response to m IL-1 beta and LPS. The hypophagic responses to mIL-1 beta and LPS were not affected by the histaminergic antagonists, pyrilamine (H-1), cimetidine (H- 2), thioperamide (H-3), or the histamine-depleting agent, alpha-fluoromethy lhistidine, nor by the muscarinic cholinergic antagonist, scopolamine. The responses to mIL-1 beta were also unaffected by the dopamine receptor antag onist, haloperidol, the opioid receptor antagonist, naloxone, and the NO sy nthase inhibitor, L-NAME. These results suggest that adrenergic, dopaminerg ic, histaminergic, cholinergic, opioid or nitric oxide systems are not esse ntial for the hypophagia induced by IL-1, and that multiple redundant pathw ays may be involved in illness-related hypophagia. (C) 1999 Elsevier Scienc e Inc.