GLUCAGON-LIKE PEPTIDE-1(7-36) AMIDES CENTRAL INHIBITION OF FEEDING AND PERIPHERAL INHIBITION OF DRINKING ARE ABOLISHED BY NEONATAL MONOSODIUM GLUTAMATE TREATMENT

In the rat, the glucagon-like peptide 1 (GLP-1)(7-36) amide inhibits n eurones in the central nervous system responsible for food and water i ntake. GLP-1-induced inhibition of food intake may involve the hypotha lamic arcuate nucleus, whereas rostral sensory circumventricular organ s may be responsible for the inhibitory action of GLP-1 on drinking. T o further investigate the role of these blood-brain-barrier-free areas in GLP-1-induced inhibition of ingestive behavior, neonatal Wistar ra ts were subjected to monosodium glutamate (MSG) treatment, which cause s extensive damage to the arcuate nucleus as well as to parts of the s ensory circumventricular organs. The inhibitory effect of GLP-1 on fee ding induced by food deprivation was completely abolished in MSG-lesio ned rats. This effect was not due to either a loss of sensitivity to a norectic agents or a loss of taste aversion because MSG-treated animal s displayed normal anorectic responses to central administration of co rticotropin-releasing factor and normal aversive responses to peripher al administration of both lithium chloride and D-amphetamine. In non-l esioned rats, neuropeptide Y (NPY)-induced feeding was significantly r educed by concomitant GLP-1 administration. In contrast, GLP-1 had no effect on NPY-induced feeding in MSG-lesioned rats, suggesting that th e GLP-1 receptors that mediate inhibition of feeding are localized ups tream to the NPY-sensitive neurones inducing feeding behavior. The inh ibitory effect of GLP-1 on water intake was tested using an ANG II-eli cited drinking paradigm. Central administration of GLP-1 inhibited ANG II drinking in both MSG-treated rats and their nontreated littermates . In contrast, peripheral administration of GLP-1 did not inhibit ANG II-induced drinking behavior in MSG-treated rats. Thus it is evident t hat centrally acting GLP-1 modulates feeding and drinking behavior via neurones sensitive to MSG lesioning in the arcuate nucleus and circum ventricular organs, respectively.