Search

The anterior piriform cortex (APC) is activated by, and is the brain area most sensitive to, essential (indispensable) amino acid (IAA) deficiency. The APC is required for the rapid (20 min) behavioral rejection of IAA deficient diets and increased foraging, both crucial adaptive functions supporting IAA homeostasis in omnivores. The biochemical mechanisms signaling IAA deficiency in the APC block initiation of translation in protein synthesis via uncharged tRNA and the general amino acid control kinase, general control nonderepressing kinase 2. Yet, how inhibition of protein synthesis activates the APC is unknown. The neuronal K(+) Cl(-) cotransporter, neural potassium chloride co-transporter (KCC2), and GABAA receptors are essential inhibitory elements in the APC with short plasmalemmal half-lives that maintain control in this highly excitable circuitry. After a single IAA deficient meal both proteins were reduced (vs. basal diet controls) in western blots of APC (but not neocortex or cerebellum) and in immunohistochemistry of APC. Furthermore, electrophysiological analyses support loss of inhibitory elements such as the GABAA receptor in this model. As the crucial inhibitory function of the GABAA receptor depends on KCC2 and the Cl(-) transmembrane gradient it establishes, these results suggest that loss of such inhibitory elements contributes to disinhibition of the APC in IAA deficiency. The circuitry of the anterior piriform cortex (APC) is finely balanced between excitatory (glutamate, +) and inhibitory (GABA, -) transmission. GABAA receptors use Cl(-), requiring the neural potassium chloride co-transporter (KCC2). Both are rapidly turning-over proteins, dependent on protein synthesis for repletion. In IAA (indispensable amino acid) deficiency, within 20 min, blockade of protein synthesis prevents restoration of these inhibitors; they are diminished; disinhibition ensues. GCN2 = general control non-derepressing kinase 2, eIF2α = α-subunit of the eukaryotic initiation factor 2.

Leptin administered intracerebroventricularly (ICV) or intrahypothalamically inhibits food intake (FI), however, to our knowledge the effects of leptin administration have only been examined in one extrahypothalamic site (dorsal raphe nucleus). Our objectives were t. (1) determine the FI effects of leptin administration into the anterior piriform cortex (APC), an area linked to the control of FI in amino acid (AA) deficiency, (2) examine leptin action during short term anorexia that develops in response to AA deficiency. Bilateral injections of leptin (0.25 μ) into the APC suppressed FI of a balanced diet between 6 and 12 h by 36% (p < 0.01) and over the first 12 and 24 h by 15% (p < 0.05). Bilateral administration of leptin (0.1 μg) inhibited FI between 12 and 24 h by approximately 48% (p < 0.05) on a threonine-imbalanced diet without significantly affecting FI on a threonine-corrected diet. The increase of plasma leptin concentrations in response to feeding a threonine-basal diet was greater than that following an AA imbalanced diet, suggesting that suppression of FI by an AA imbalanced diet is not mediated by an increase of leptin. Our results suggest that (1) administration of leptin into a brain area outside the hypothalamus suppresses FI, and (2) leptin is unlikely to play a selective role in the short term anorectic response to AA deficiency. These data are consistent with the hypothesis that endogenous leptin can act within the APC to modulate FI.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.tins.2005.12.007 Byline: Dorothy W. Gietzen (a), Quinton R. Rogers (b) Abstract: Indispensable amino acids are neither synthesized nor stored in animals and are rapidly depleted when not provided by the diet. To maintain homeostasis, organisms must sense deficiency of an indispensable amino acid and implement a repletion strategy. In rats and birds, the anterior piriform cortex houses the detector, but its mechanism has evaded description for >50 years. Recently, rapid detection of amino acid depletion was shown behaviorally when naA[macron]ve animals, pre-fed a low nitrogen diet, terminated their first deficient meal within 20min. The general amino acid control system of yeast, which is activated by amino acid deprivation via deacylated tRNA, was found to be active in rodent brain, showing conservation of amino acid sensory mechanisms across eukaryotic species. Author Affiliation: (a) Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, One Shields Avenue, University of California, Davis, CA 95616, USA (b) Department of Molecular Biosciences, School of Veterinary Medicine, One Shields Avenue, University of California, Davis, CA 95616, USA

Transition from a normal- (NP) to a high-protein (HP) diet induces a rapid depression in food intake and a progressive but incomplete return to the initial intake during the succeeding days. The aim of this study was to determine which CNS regions are involved in the HP diet-induced satiety in rats. Brains were collected from 3 groups of adult rats after habituation to an NP diet (21 d), during the transition phase to a HP diet (2 d), or after habituation to the HP diet (21 d). Fos expression was measured in several brain areas that are involved in the control of food intake (solitary tract nucleus, anterior piriform cortex, lateral hypothalamus, arcuate nucleus, posterior para ventricular nucleus, medio ventral hypothalamus, dorso medial hypothalamus, amygdala, and accumbens nucleus). Changes occurred in the majority of these regions during the transition period from the NP diet to the HP diet. After habituation to the HP diet, significant changes in Fos expression were restricted to an increase in the nucleus of the solitary tract and a decrease in the ventromedial hypothalamus and the cortex of the amygdala. Considering the functional characteristics of these areas, the present results suggest that the vagus nerve conveys the information relative to the quantity of protein ingested, that hypothalamic sites regulate food intake and may alter sympathetic nervous system activity, and that higher brain functions such as memory processing by the limbic system or food reward system are involved in the HP diet-induced satiety in rats. KEY WORDS: * brain * vagus nerve * satiety * protein

Diets deficient in an indispensable amino acid have long been known to suppress food intake in rats. Detection of dietary deficiency takes place in the anterior piriform cortex (APC). Recent studies showed that the response to amino acid deficiency takes as little as 15 min to develop, but few data exist to correlate the concentration of amino acids in the APC with this rapid response. The purpose of this study was to measure the concentration of amino acids in the APC in a behaviorally relevant time frame. Rats were preconditioned by consumption of a basal diet for 7-10 d, and then given a test diet with either a control or deficient amino acid profile. Both the threonine- and leucine-deficient diets reliably depleted threonine and leucine concentration in the APC within 30 min, respectively. The control diets and a diet lacking the dispensable amino acid glycine did not lead to amino acid depletion. In combination with previous studies, the present results show that the decrease in the concentration of indispensable amino acids in the APC may be the initial sensory signal for recognition of dietary amino acid deficiency. KEY WORDS: * amino acid imbalance * anterior piriform cortex * threonine * leucine

Sensing of indispensable amino acid (IAA) deficiency, an acute challenge to protein homeostasis, is demonstrated by rats as rejection of IAA-deficient diets within 20 min. The anterior piriform cortex (APC) of the brain in rats and birds is essential for this nutrient sensing, and is activated by IAA deficiency. Yet the mechanisms that sense and transduce IAA reduction to signaling in the APC, or indeed in any animal cells, are unknown. Because rejection of a deficient diet within 20 min is too rapid to be explained by transcription-derived signals, brain tissue was taken from rats after 20 min access to either a threonine-basal, -devoid, or -corrected diet and examined for proteins associated with early signaling of IAA deficiency in the yeast model. Western blots and immunohistochemistry showed that the phosphorylation of eukaryotic initiation factor 2-[alpha] (p-elF2[alpha][Ser51]) and translation of its downstream product, c-Jun, were increased (47%, P < 0.005, and 55%, P < 0.025, respectively) in APC from rats offered devoid, but not corrected diets, compared with those offered basal diets. This was not seen in other brain areas, in cells intensely labeled for cytoplasmic p-elF2c[alpha], there was intense fluorescence for c-Jun in the nucleus. Thus, p-elF2[alpha], which is pivotal in the initiation of global protein translation, and its downstream product, the leucine zipper protein, c-Jun, are increased in the mammalian APC within the time frame necessary for the behavioral response. We suggest that p-elF2c[alpha] and c-Jun participate in signaling nutrient deficiency in the IAA-sensitive neurons of the APC. KEY WORDS: * nutrient sensor * translation initiation * feeding behavior * essential amino acids * c-Jun

Omnivores must obtain diets balanced with respect to amino acids to support growth and protein synthesis. The standard paradigm used to study behavioral responses to amino acid deficiency combines deficient diets with dietary novelty. The objective of this study was to examine the effects of amino acid deficiency on the first meal of rats without the confounding effects of novelty. We report on a series of five studies of feeding behavior in rats. Rats were fed low protein diets for 5-7 d and then exposed to diets with and without essential amino acids. Rats consistently demonstrated recognition of essential amino acid deficiency within the first meal by a significant reduction in first meal duration, rejecting the deficient diets after just 12-16 min exposure. This is the first report of a rapid effect of amino acid-deficient diets without the confounding effects of dietary novelty. KEY WORDS: * amino acid imbalance * feeding behavior * rodents * microstructure

Omnivores show recognition of essential (indispensable) amino acid deficiency by changing their feeding behavior within 20 min, yet the cellular mechanisms of amino acid sensation in eukaryotes are poorly understood. The anterior piriform cortex (APC) of the brain in rats or its analog in birds likely houses the in vivo amino acid chemosensor. Because amino acid transporters adapt rapidly to essential amino acid deficiency in several cell models, we hypothesized that activation of electrogenic amino acid transport in APC neurons might contribute to the function of the amino acid sensor. We evaluated transport systems in primary cultures of neurons from the APC, hippocampus and cerebellum, or glia, incubated in complete or threonine-devoid (deficient) medium. After 10 min in deficient medium, uptake of threonine or a system A-selective substrate, methyl amino-isobutyric acid, was increased 60% in APC neurons only (P < 0.05). These results demonstrated upregulation of system A, an electrogenic amino acid-sodium symporter. This depletion-induced activation required sodium, intact intracellular trafficking, and phosphorylation of signal transduction-related kinases. Efflux studies showed that other transporter types were functional in the APC; they appeared to be altered dynamically in threonine-deficient cells in response to rapid increases in system A activity. The present data provided support for the chemical sensitivity of the APC and its role as the brain area housing the indispensable amino acid chemosensor. They also showed a region-specific, phosphorylation-dependent activation of the system A transporter in the brain in response to threonine deficiency. KEY WORDS: * deficiency * nutrient sensor * brain * amino acid * neuron culture

The anterior piriform cortex (APC) is essential for the anorectic reactions to an amino acid-imbalanced diet, and it also responds to repletion of the limiting amino acid. In the present study, we examine the dynamic changes of the interstitial dopamine metabolites in the APC following feeding of either an amino acid-corrected or -imbalanced diet. Microdialysates, collected from the APC, were analyzed using HPLC with electrochemical detection. The concentrations were 19.7 [+ or -]4.8 [[micro]gram]/L for 3,4-dyhydroxyphenylacetic acid and 25.1 [+ or -] 4.4 [[micro]gram]/L for homovanillic acid, respectively, in the baseline dialysates. After diet treatments, no significant changes occurred in 3,4-dyhydroxyphenylacetic acid in the corrected (n = 7) or imbalanced (n = 9) groups vs. the basal group (n = 7). However, after feeding the threonine-corrected diet, the concentration of homovanillic acid was significantly less (P < 0.01) than after the basal and imbalanced diets. The homovanillic acid level in the corrected group was already significantly lower than in the basal group by 20 min (P < 0.05), and reached its lowest level at 70 min (P < 0.05). The concentrations of homovanillic acid in the corrected group remained at this low level until the end of the experiment. The present results introduce the idea that the dopaminergic system is involved in the feeding responses to essential amino acid repletion. KEY WORDS: aversion; feeding; microdialysis; monoamine; rats

Rats can adjust their nutrient intake in response to nutritional deficiency. This phenomenon has been described extensively for sodium deficiency, whereas other nutrient deficiencies have not been explored thoroughly. Essential amino acid (EAA) deficiency represents a relevant model to describe adaptive changes in behavior resulting from deficiency. The purpose of these experiments was to examine more closely the behavioral responses that occur as a result of lysine (LYS) and threonine (THR) deficiency. Licking to LYS, THR, glycine and distilled water during 10-s trials was measured in control (CON) and EAA-deficient rats. Licking tests were conducted both before and after 23-h intake tests. Although EAA-deficient rats did not show increased licking to the deficient EAA in any of the brief-access tests, in all cases, they did initiate significantly more overall trials than did CON. The EAA-deficient rats also had elevated intake of the deficient EAA in long-duration tests. These findings suggest that LYS or THR deficiency does not emulate the behavioral properties of sodium deficiency in that it does not result in enhanced immediate licking responses to the limiting EAA in brief-access tests. Nevertheless, an appetite is expressed to the relevant EAA in a long-term intake test. KEY WORDS: lysine; threonine; specific appetite; 23-h intake; rats

A study was conducted to determine the relationship between cholecystokinin (CCK) and serotonin (5-HT) in fat-induced satiety in rats. Selective receptor antagonists were used in the study to elucidate the roles of the two chemical modulators in fat-induced satiety. The antagonists Devazepide and Tropisetron were found in combination to completely block the satiating effects of the 80% fat infusate on all feeding variables that were measured. The results suggest that both endogenous 5-HT and CCK play a role in the satiety response to fat in the intestine.

Under states of protein deficiency, the dietary limiting amino acid, rather than protein content, can act as the dietary stimulus to control diet selection. If fact, threonine-deficient rats will alter their diet selection patterns solely on the basis of very small changes (0.009 g/100 g) in the dietary threonine concentration. In these studies, we assessed whether lysine-deficient rats will also alter their diet selection patterns on the basis of small changes in dietary Lys concentration. In all experiments, growing rats were adapted to diets in which the protein fraction (purified amino acids or wheat gluten) was limiting in Lys. They were then given a choice between the adaptation diet (AD) diet and a slightly more deficient diet. Rats that were adapted to a Lys-deficient diet (0.25 g Lys/100 g) selected their AD over diets containing as little as 0.01% less Lys (P < 0.01) within 5 d. To determine how deficient rats must be before they alter their selection patterns, rats were adapted to diets containing various levels of Lys, i.e., 2 levels below the requirement for growth and 2 levels above the requirement for growth, but below the requirement for maximal nitrogen retention. Only rats adapted to diets containing Lys below their requirement for growth selected their AD over a diet containing 0.05% less Lys (P < 0.005). Finally, to determine whether rats will alter their selection to whole protein-based diets, rats were adapted to 25% wheat gluten diets supplemented with 0.03-0.21% Lys. Rats selected the AD over a diet containing as little as 0.09% less supplemental Lys by d 4 of the trial (P < 0.05). We conclude that rats are sensitive to changes as small as 0.01% in dietary Lys concentration, but that sensitivity requires prior adaptation to Lys-deficient diets. KEY WORDS: lysine, deficiency, food intake, diet selection, amino acid requirements, rats

The changes in feeding patterns underlying decreased food intake near the end of life of rats are described. The nine male rats whose meal patterns associated with age-related decline in food intake exhibited a similar pattern of decreased food intake. While they ate smaller meals, there was no difference in the number of meals they ate per day. Their selection of preferred diets was not affected by rapid weight loss.

Vitamin B-6 is a cofactor in many reactions of nitrogen metabolism. Deficiency alters tissue amino acid concentrations but effects of excess vitamin B-6 have not been well described. We fed female rats (218 g, 7 per group) 1 (control), 10, 100, 175 or 250x) the National Research Council recommended level of pyridoxine HCl (7 mg/kg) for 10 wk and measured serum amino acids, amino acids and neurotransmitters in brain regions and the binding properties of serotonin receptors in the cerebral cortex using a ketanserin binding assay. Rats were decapitated, and unheparinized blood was obtained. In the caudate nucleus, concentrations of glutamate, threonine, taurine, methionine, [Gamma]-amino-butyric acid and the sum of the essential amino acids in groups 10X and 100X were [approximately]130 to 180% of control levels (P < 0.05); groups 1X, 175X and 250X were not different. A similar pattern was seen in the serum for serine, glycine, aspartate and ornithine; the latter two amino acids increased to over 200% of control in group 100X. In the ketanserin binding assay, both the antagonist binding affinity and the maximal number of binding sites were higher for group 100X than for 1X, 175X and 250X, and were higher for 10X than for 1X. Norepinephrine in the raphe nucleus followed a similar biphasic pattern. Excess dietary pyridoxine affected brain and serum concentrations of some amino acids and binding properties of cortical serotonin receptors in a biphasic pattern over the range of concentrations fed in this study. KEY WORDS: * vitamin B-6 * amino acids * brain * blood * rats

A study was conducted to test whether the hyperphagia feature of obese (fa/fa) rats supports impaired neural cholecystokinin (CCK) secretion. The rats were anesthetized with a ketamine-xylazine-acepromazine cocktail while fixed brains were sectioned on a cryostat and stained with cresyl violet. Results indicated that hypothalamic CCK supports a physiological function in satiety. Findings also showed that Zucker rats have blunted hypothalamic CCK release based on dietary cues.

Within 3 h of ingesting an imbalanced amino acid diet (IAAD), rats show attenuated intake. The associated conditioned taste aversion can be ameliorated by giving the [serotonin.sub.3] receptor blocker, tropisetron (TROP). A recent c-fos study indicated that the dorsomedial hypothalamic nucleus (DMN) may be activated 2-3 h after ingestion of IAAD. In Experiment 1, DMN-lesioned rats (DMNL) or sham-operated (SHAM) rats were injected with saline (SAL) or TROP just before introduction of IAAD. By 3 h, SAL-DMNL rats consumed more (P < 0.01) of the IAAD than did the SAL-SHAM rats. Thereafter, over the next 21 h, the intake of the SAL-DMNL group returned to control levels. TROP treatment enhanced the intake of the treated groups; the TROP and the lesion effect were additive (P < 0.01). By d 4 of receiving the IAAD, the DMNL groups were eating less than SHAM rats (P < 0.05). The data suggest that the DMN may be involved in the early detection of the amino acid deficiency induced by IAAD, is not involved in the TROP effect and is necessary for proper long-term adaptation to an IAAD. KEY WORDS: body weight; [serotonin.sub.3] receptors; feeding; rats; essential amino acid deficiency

Amino acid-imbalanced (IMB) diets induce an acute amino acid deficiency and hypophagic responses in most animals. The neural circuits underlying these responses are unknown. To ascertain potential neural circuits involved in the recognition of IMB, we measured the concentrations of norepinephrine, dopamine, serotonin, their metabolites and 20 amino acids in 14 rat brain areas in three studies. Rats were prefed a basal diet with L-amino acids as the protein source for at least 1 wk. For the experiments, either threonine or isoleucine IMB diet was offered for 2.5 or 3.5 h. Brains were taken before (using a mildly IMB diet) or after (using moderately or severely IMB diet) food intake was significantly (P < 0.05) depressed. Brain areas were dissected and analyzed for monoamines, metabolites and amino acids. Only in the anterior piriform cortex (APC), a brain area that may contain the amino acid chemosensor, was the limiting amino acid lower in IMB groups than in controls across all of the experiments. Before the onset of the anorectic response to the IMB diets, monoaminergic activity was affected in areas that have recognized monosynaptic connections with the APC. We propose a circuit for the neural responses in the initial recognition of acute amino acid deprivation that begins with activation of the APC and includes areas in the hindbrain and hypothalamus. After a significant hypophagic response, serotonergic indicators were altered in areas of the taste pathway and the limbic system. These results suggest that different circuits mediate the initial recognition and secondary conditioned responses to IMB diets. KEY WORDS: rats; feeding behavior; monoamines; chemosensor; conditioned aversion

Research shows that the feeding patterns of Wistar rats are affected after receiving infusions of carbohydrate, fat and protein. Experiments designed to identify the impact of various feed mixtures on the quality and quantity of rat feeding habits using casein hydrolysate infusions are described. Food intake measurements were recorded and analysed using computer technology.

The rat's sensitivity to changes in the dietary limiting amino acid concentration (LAA) was examined on the basis of dietary selection. Rats were adapted to purified low protein basal (Basal) diets in which threonine (Thr) was the LAA (0.188-0.212% wt/wt of diet). In Experiment 1, rats made a clear selection for their adaptation diet over a diet containing 0.012% less threonine after 2-3 d of choice. Rats made no clear dietary selection when given a choice between their adaptation diet and a diet containing 0.012% more threonine. Experiment 2 was conducted to examine the rat's sensitivity to small decreases in the LAA concentration. Rats adapted to a 0.200% Thr-Basal diet clearly responded to decreases as small as 0.009% in the concentration of threonine and selected against the more deficient diet when given a choice between it and the 0.200% Thr-Basal adaptation diet. Because plasma and brain amino acid concentrations are important for detection of other amino acid deficiencies, these variables were measured to determine whether they were affected by such small changes in dietary amino acid concentration. in Experiments 3 and 4, rats were adapted to the 0.200% Thr-Basal diet and then fed 0.188, 0.200 or 0.212% Thr-Basal diets for 6 h, or 0.188 and 0.212% Thr-Basal for 54 h. Amino acid concentrations in plasma, prepiriform cortex and anterior cingulate cortex were not significantly different among treatments. Norepinephrine concentration in the prepiriform cortex was not affected by dietary treatment. We conclude that small decreases in LAA concentration can cause selection against the more deficient diet, but that detection of such deficiencies does not require significant changes in plasma and brain amino acid concentrations. KEY WORDS: * amino acid deficiency * threonine * food intake * diet selection * rats

The relationship between acute indispensable amino acid deficiency (IAA) induced by amino acid imbalanced diets and vulnerability to chemically induced seizures was investigated in a model using rats with experimentally-induced epilepsy. During IAA, rats showed an increase in activity in the anterior piriform cortex (APC), a region of the brain that is prone to seizures. Amino acid-deficient animals showed increased susceptibility to seizures compared to controls, suggesting that IAA deficiency is associated with activation of APC.

Rats offered an amino acid-imbalanced diet (IMB) respond to the ensuing amino acid deficiency rapidly with a decrease in food intake of at least 50%. Pretreatment with tropisetron (TROP), an antagonist at [serotonin.sub.3] (5-H[T.sub.3]) and 5-[HT.sub.4] receptors, increases intake of IMB to approximately 85% of control. Vagotomy has two effects: it increases intake of an IMB to about 65%, and also blocks the increased response to tropisetron. This indicates that the greater IMB intake after tropisetron, [approximately] 20% more than in vagotomized rats, is dependent on an intact vagus. Rats were either 1) vagotomized or sham-operated, or 2) given tropisetron or saline injections. We then examined free-feeding meal patterns in rats fed an IMB to determine whether the microstructure of the feeding behavior differed, either between treatments, or by comparison with the meal patterns in rats fed the control diet. Vagotomy did not alter meal patterns in rats consuming the basal control diet. During the first 6 h after introduction of the IMB, the control rats showed significantly longer intermeal intervals (over twice the length of intervals recorded in those fed the basal diet), with corresponding effects on meal numbers, which were restored to basal values in tropisetron and vagotomized rats. Meal size was increased after vagotomy also. After 6 h, in intact tropisetron-treated rats only, a fourfold faster rate of eating throughout the late dark period accounted for the significantly greater intake of the IMB than in controls. The results demonstrated differential effects of the two treatments on the anorectic responses to amino acid deficiency. J. Nutr. 126: 1722-1731, 1996. INDEXING KEY WORDS: * amino acid imbalance * essential amino acids * rats * feeding behavior * serotonin

Research on the influence of vagus nerve and the serotonin3 (5-HT3) receptor on the mediation of food intake depression, related to amino acid inadequacy in rats fed with isoleucine-imbalanced (IMB) diet, reveals an increase in IMB intake due to 5-HT3 antagonist tropisetron treatment. The vagal physiological system participates in the anorectic responses to IMB. Establishment of the complete effect of 5-HT3 antagonists in the weakening of anorectic response to IMB requires intact vagal function.

Food intake is rapidly and reliably reduced when animals are offered diets that result in an essential amino acid deficiency, such as those used in the imbalanced amino acid diet (IMB) paradigm. There seem to be at least three phases in the responses of rats to IMB: 1) In order to respond to a dietary challenge, the animals must first recognize that challenge. The available data suggest that before the behavioral effects occur, a decline in the concentration of an essential amino acid is sensed in a specific brain area, the prepyriform cortex. This recognition phase is associated with localized decreases in the concentrations of the limiting amino acid, norepinephrine and cyclic AMP and with altered protein synthesis. 2) Subsequent to recognition of the deficiency, a conditioned taste aversion develops, mediated in part by serotonin at the level of the vagus. 3) Finally, in the absence of a choice, the animals adapt to an IMB (but not a diet devoid of one or more essential amino acids) in similar to 1 wk. Damage to certain extrahypothalamic brain areas or liver denervation accelerates adaptation to IMB, suggesting both central and peripheral control in the adaptation phase. The resulting behavioral responses provide adaptive advantage to an animal in the selection of a diet with an appropriate balance of amino acids. J. Nutr. 123: 610-625, 1993.

Differential effects of selective vagotomy and tropisetron in aminoprivic feeding. Am J Physiol Regulatory Integrative Comp Physiol 279: R997-R1009, 2000.--Both total subdiaphragmatic vagotomy (TVAGX) and [serotonin.sub.3] receptor blockade with tropisetron or ondansetron attenuate amino acid-imbalanced diet (Imb) anorexia. Total vagotomy is less effective than tropisetron in reducing Imb-induced anorexia and also blunts the tropisetron effect. With the use of electrocautery at the subdiaphragmatic level of the vagus, we severed the ventral and dorsal trunks as well as the hepatic, ventral gastric, dorsal gastric, celiac, and accessory celiac branches separately or in combination to determine which vagal branches or associated structures may be involved in these responses. Rats were prefed a low-protein diet. On the first experimental day, tropisetron or saline was given intraperitoneally i h before presentation of Imb. Cuts including the ventral branch, i.e., TVAGX, ventral vagotomy (above the hepatic branch), and hepatic + gastric vagotomies (but not hepatic branch cuts alone) caused the highest (P [is less than] 0.05) Imb intake on day 1 with or without tropisetron. The responses to tropisetron were not. affected significantly. On days 2-8, groups having vagotomies that included the hepatic branch recovered faster than sham-treated animals. Because the hepatic and gastric branches together account for most of the vagal innervation to the proximal duodenum, this area may be important in the initial responses, whereas structures served by the hepatic branch alone apparently act in the later adaptation to Imb. amino acid; diet; amino acid-imbalanced diet; amino acid deficiency; rat; food intake; body weight; vagus; serotonin