PharmacologyBiochemistry and Behavior, Vol.43, pp. 847-854, 1992 0091-3057/92$5.00 + .00 Printedin the U.S.A. All rightsreserved. Copyright© 1992 Pergamon PressLtd. Peripheral Serotonin is an Incomplete Signal for Eliciting Satiety in Sham-Feeding Rats K. J. SIMANSKY, l J. JAKUBOW, 2 F. C. SISK, A. H. VAIDYA 3 AND K. EBERLE-WANG Medical College of Pennsylvania at Eastern Pennsylvania Psychiatric Institute, Philadelphia, PA 19129 Received 23 January 1992 SIMANSKY, K. J., J. JAKUBOW, F. C. SISK, A. H. VAIDYA AND K. EBERLE-WANG. Peripheral serotonin is an incomplete signalfor eliciting satiety in sham-feeding rats. PHARMACOL BIOCHEM BEHAV 43(3) 847-854, 1992.- Peripheral administration of serotonin [5-hydroxytryptamine (5-HT)] to rats equipped with gastric cannulae reduced their 30-rain consumption of sweetened milk after overnight deprivation whether the cannniae were closed (real feeding) or open (sham feeding). The anorectic action of 5-HT (1.6, 4.0, and 10.0 #mol/kg, IP) in sham feeding was dose-related, rapid in onset, and persisted during the 30-rain 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 #mol/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 selectivebecause 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. Serotonin 5-Hydroxytryptamine Peripheral serotonin Feeding Anorexia Satiety Sham feeding Sham drinking Exploration ENDOCRINE and neuronal cells within the gastrointestinal system synthesize high concentrations of the biogenic amine serotonin [5-hydroxytryptamine (5-HT)] (12,22). Accordingly, a considerable amount of interest has developed for testing whether 5-HT from the gut might provide a signal for the short-term control of feeding. Using systemic administration as a probe for this function, 5-HT (9,21,29) and some of its peripherally acting analogs (13,26,27) reduced food intake by rats under a variety of testing conditions. This anorectic action occurred at doses of 5-HT that did not act as unconditional stimuli for a conditioned taste aversion or impair sensorimo- tor performance (9,21). Thus, 5-HT apparently reduced food intake by a selective action on feeding rather than by some nonspecific behavioral effect. Analysis of log-survivor func- tions in deprived rats consuming pellets suggested that 5-HT lowered intake by reducing the size and duration of bouts of feeding (10). In a runway task using food-deprived rats, 5-HT decreased running speed only after some pellets were con- sumed (8). The slowing of the running paralleled the decay of the cumulative food intake curve. Overall, these data implied that 5-HT decreased the consumption of food by selectively enhancing the satiety effect of ingested food or of feeding. The influence of 5-HT on the process(es) leading to satia- tion can be examined more precisely during sham feeding us- ing rats equipped with gastric cannulae. In a previous study (18), 5-HT reduced gastric sham feeding of a sucrose solution without altering sham drinking. This effect on the consump- tion of liquid diet was consistent with the idea that peripher- ally administered 5-HT interacted with oropharyngeal stimuli associated with food or feeding to enhance satiety. Additional information about the role of 5-HT in terminating a meal would be revealed, however, by analyzing the nature of the behavioral changes associated with the anorectic action of 5- HT. If exogenous 5-HT probes a function for this indoleamine in satiety, then peripheral serotonergic stimulation should not only reduce food intake but also accelerate the sequence of nonfeeding activities and resting typical of satiation (1). In a recent study using observational analysis (7), rats given 5-HT subcutaneously did stop feeding sooner and displayed behav- ioral evidence of satiety more quickly than controls. It remains to be determined, however, whether 5-HT would exert a simi- lar action in sham-feeding rats. Comparing the efficacy of 5-HT to produce behavioral satiety during sham and normal feeding would assess the importance of gastrointestinal stimuli for this serotonergic effect. The present investigation, therefore, determined the ac- 1 Requests for reprints should be addressed to K. J. Simansky, Ph.D., Department of Pharmacology, Medical College of Pennsylvania/EPPI, 3200 Henry Avenue, Philadelphia, PA 19129. 2 Current address: Department of Psychology, Queens College of CUNY, Flushing, NY 11367. 3 Current address: R. W. Johnson Pharmaceutical Research Institute, CNS Research/Drug Discovery, R314, Springhouse, PA 19477. 847