Intake inhibition by NPY: role of appetitive ingestive behavior and aversion.

Intraventricular infusion of neuropeptide Y (NPY) decreases the amount female rats ingest during intraoral infusion (consummatory behavior) of a 1-M solution of sucrose at a rate of 0.5 ml/min and simultaneously increases the number of times the rats visit a bottle filled with sucrose (appetitive behavior). In this study, we investigated if the suppression of consummatory behavior was dependent upon the increase of appetitive behavior. The shift from consummatory to appetitive ingestive behavior was attenuated by adding 3-mM quinine HCl (QHCl) to the sucrose solution in the bottle. However, the intraoral intake of the sucrose solution was still decreased in NPY-treated rats. NPY did not modify taste reactivity as measured by aversive responses during continuous intraoral infusion of sucrose or ingestive and aversive responses to brief intraoral infusion of sucrose (0, 0.3 or 1 M) or QHCl (0, 0.3 or 3 mM). NPY stimulated visits to a bottle and intake from the bottle and inhibited sexual behavior in male rats but had no effect on the sexual behavior in the absence of a bottle. The visits and the intake were suppressed, but sexual behavior was not activated by adding QHCl (3 mM) to the solution in the bottle. Obstructing appetitive ingestive behavior, therefore, does not indiscriminately facilitate consummatory behavior. Male rats showed aversive or ingestive behavior and sexual behavior simultaneously during intraoral infusion of QHCl or condensed milk. It is suggested that NPY decreases intraoral intake and increases appetitive ingestive behavior via partially separable mechanisms that are independent of taste aversion.

Dopamine D(2) receptors and ingestive behavior: brainstem mediates inhibition of intraoral intake and accumbens mediates aversive taste behavior in male rats.

RATIONALE: One of the factors that terminate the ingestion of an intraorally infused solution of sucrose may be an increase in the perceived aversiveness of its taste. OBJECTIVES: We tested the hypothesis that dopamine D(2), as opposed to D(1), receptors in the brainstem or nucleus accumbens inhibit intraoral intake by enhancing the aversiveness of the taste of the infused solution. METHODS: Male rats were infused intraorally with a 2 M sucrose solution (1 ml/min) and intake and the display of gapes and chin rubs, i.e. taste-related aversive behavior, was measured. Gapes and chin rubs were also measured in rats during and 40 s after brief intraoral infusion (1 ml/min during 20 s) of a 0.3 mM solution of quinine HCl. The full D(1) receptor agonist dihydrexidine (0.1-3.0 mg/kg) and antagonist SCH-23390 (0.03-0.1 mg/kg), the D(2) receptor agonist quinpirole (0.3 mg/kg) and antagonist raclopride (1.7 mg/kg) were injected IP. Quinpirole (14-55 microg) and raclopride (5 microg) were also infused into the fourth brain ventricle. In addition, quinpirole (2 or 10 microg) was infused into the shell region of the nucleus accumbens. RESULTS: IP dihydrexidine and quinpirole inhibited the intraoral intake of sucrose and pretreatment with raclopride, but (in the case of dihydrexidine) not SCH-23390, attenuated this effect. Injection of quinpirole into the fourth ventricle produced raclopride-reversible inhibition of intraoral intake but did not stimulate the display of gapes and chin rubs. Infusion of quinpirole into the shell region of the nucleus accumbens had the opposite effects. The intake of sucrose was suppressed by the addition of quinine HCl but this suppression was unaffected by dopamine agonist or antagonist treatment. CONCLUSIONS: It is suggested that brainstem dopamine D(2) receptors mediate suppression of consummatory ingestive behavior and that D(2) receptors in the shell region of the nucleus accumbens mediate the display of gapes and chin rubs, but that neither of these D(2) receptor populations mediate the hedonic evaluation of taste.

Acute effects of peritoneal dialysis solutions on appetite in non-uremic rats.

BACKGROUND: Standard peritoneal dialysis (PD) solutions may contribute to anorexia in PD patients due to the peritoneal absorption of glucose from the dialysate, abdominal discomfort and other factors. New PD solutions containing alternative osmotic agents, neutral pH and bicarbonate as buffer were recently developed. To test the effect of these solutions on appetite, we investigated how intraoral (IO) intake of sucrose via an IO cannula was influenced by intraperitoneal (IP) infusion of different PD solutions in an appetite model in rats. METHODS: The IO intake was measured in male Wistar rats after an IP dwell of 30 and 120 minutes with the following PD solutions: 1.36%, 2.27% and 3.86% glucose based and lactate buffered solutions (D); 1.36%, 2.27% and 3.86% glucose based and bicarbonate/lactate buffered solutions (P); 7.5% icodextrin based solution (E); 1.1% amino acid-based solution (N); and, 2.5% glucose-based lactate-buffered solution (GB), using sham injection (injection without infusion) as control. Prior to the tests, rats were provided with an IO cannula, and were trained for two weeks until the rate of IO intake had stabilized. RESULTS: The D and N solutions inhibited IO intake. For the D solutions, the degree of appetite suppression was higher with the higher concentration of glucose. P 3.86%, but not P 1.36% and P 2.27% solutions, inhibited the IO intake. However, a comparison of the degree of appetite inhibition between D and P showed less inhibition with P 1.36%, 2.27% and 3.86% solutions than with corresponding D solutions. The E solution did not seem to suppress appetite. Finally, no significant difference in IO intake was found between rats given GB 2.5% and D 2.27%. CONCLUSIONS: In this appetite model in rats, the measurement of IO intake after the IP infusion of different dialysis solutions showed that (1) N and D solutions may reduce appetite, and for the D solutions the degree of appetite inhibition was related to the dialysate concentrations of glucose; (2) the P solutions had less impact on appetite than the D solutions; (3) the E solution had no impact on appetite during the short dwells of 30 and 120 minutes. The demonstrated differences between the different solutions appear to be due to different concentrations, and type, of nutrients used as osmotic agent (glucose, amino acids, icodextrin) or buffer (lactate), although differences in dialysate pH, tonicity and concentration of glucose degradation products also may be important. The present studies suggest a possible positive effect on appetite by using bicarbonate/lactate buffered solutions instead of lactate buffered solutions.

Aversive behavior during intraoral intake in male rats.

We investigated if the taste of a sucrose solution becomes progressively more aversive during intraoral infusion and if this contributes to the termination of the intake in male rats. The display of aversive behavior, such as gapes and chin rubs, but not headshakes, forelimb flails or orofacial grooming, varied with the concentration of an intraorally infused solution of quinine hydrochloride (QHCl) and increased by the time the rat rejected an intraorally infused 2 M solution of sucrose. Activation of gapes and chin rubs by brief intraoral infusion of QHCl advanced the rejection of the sucrose solution if given late during intraoral infusion, but blockade of gaping by anaesthesization of the oral cavity with Xylocain did not prolong the intake of the sucrose solution. Headshakes and forelimb flails could be elicited by stimulating the head and limbs with sucrose, and gapes and chin rubs were activated by infusion of a 2 M solution of sucrose into the stomach or duodenum but not by infusion of glucose into the jugular or hepatic portal vein. Preventing filling of the gastrointestinal tract during intraoral infusion of sucrose (sham feeding) eliminated the display of gapes and chin rubs. It is suggested that an increase in the aversiveness of the taste of a sucrose solution contributes to the rejection of that solution during intraoral infusion. However, rats can reject a sucrose solution in the absence of any behavioral sign of aversion and none of the so-called "taste-related" aversive behaviors is exclusively dependent upon stimulation of the taste receptors in the oral cavity.

NPY-leptin: opposing effects on appetitive and consummatory ingestive behavior and sexual behavior.

Many studies have indicated that neuropeptide Y (NPY) stimulates and leptin inhibits food intake. In line with this, intracerebroventricular injection of NPY (10 microg) stimulated and leptin (10 microg) inhibited intake of a sucrose solution when female rats were required to obtain the solution from a bottle. However, NPY inhibited and leptin stimulated intake if the solution was infused intraorally. Thus NPY stimulates the responses used to obtain food but inhibits those used to consume food, and leptin has the opposite effects. To test the specificity of these responses the sexual behavior of male rats was examined. NPY-treated males showed minor deficits in sexual behavior but chose to ingest a sucrose solution rather than copulate with a female if offered the choice. By contrast, leptin-treated males ingested little sucrose and displayed an increase in ejaculatory frequency if given the same choice. It is suggested that NPY is not merely an orexigenic peptide, but one that directs attention toward food. Similarly, leptin may not be an anorexic peptide, but one that diverts attention away from food toward alternate stimuli.