Peripheral serotonin is an incomplete signal for eliciting satiety in sham-feeding rats.

Peripheral administration of serotonin [5-hydroxytryptamine (5-HT)] to rats equipped with gastric cannulae reduced their 30-min consumption of sweetened milk after overnight deprivation whether the cannulae were closed (real feeding) or open (sham feeding). The anorectic action of 5-HT (1.6, 4.0, and 10.0 mumol/kg, IP) in sham feeding was dose-related, rapid in onset, and persisted during the 30-min testing session. However, 5-HT failed to elicit resting--the terminal behavioral phase of satiety--in sham-feeding rats. Direct comparison of the effects of 4.0 mumol/kg 5-HT under both feeding conditions established that this dose promoted resting only when rats fed with their cannulae closed. The actions of 5-HT on feeding and resting were behaviorally selective because serotonergic treatment did not retard the beginning of feeding, alter sham drinking of water, or reduce investigation by food-deprived rats of a novel object in an open field. Together, the results suggest that 5-HT exerts separate actions to inhibit feeding and accelerate the process of satiation as marked by resting. However, peripheral 5-HT is inadequate as a signal for modulating satiety in the absence of postingestive stimuli.

Peripherally administered alpha-methyl-5-hydroxy-tryptamine and 5-carboxamidotryptamine reduce food intake via different mechanisms in rats.

Peripherally administering the serotonin (5-HT) analogs, alpha-methyl-5-hydroxytryptamine (alpha-Me-5-HT) and 5-carboxamidotryptamine (5-CT), reduced milk consumption by food-deprived rats. 5-CT decreased milk intake 100-fold more potently than alpha-Me-5-HT (ID(50)'s =.06 and 5.6µmol/kg, respectively). 5-CT also elicited drinking but alpha-Me-5-HT did not. The nonselective 5-HT antagonist, methysergide, blocked the anorectic actions of each agonist. By contrast, the 5-HT(2) antagonist, ketanserin, and the peripheral 5-HT(2) antagonist, xylamidine, only prevented anorexia due to alpha-Me-5-HT. These results suggest that stimulating either peripheral 5-HT(2) or peripheral 5-HT(1)-like receptors inhibits feeding in rats. 5-HT(1)-like sites may also mediate 5-HT-induced drinking.