Increased short­term food intake after external lateral parabrachial subnucleus lesions in rats.

The vagus nerve and several brainstem nuclei to which it projects have been closely associated with food intake. The aim of this study was to determine the degree to which the same or different information on food intake is processed by this nerve and by one of these nuclei, the external lateral parabrachial subnucleus (LPbNe). For this purpose, we analyzed the solid and liquid food intake of Wistar rats subjected to vagal deafferentation with capsaicin or lesions of the LPbNe. Vagotomized animals consumed significantly larger amounts of solid food during the first 24 h post­surgery but not at 48, 72, or 96 h. Animals with LPbNe lesions also consumed larger amounts of liquid and solid foods but only during periods of 60 min on day 5 and 90 min on day 6 post­surgery, respectively. According to these findings, both the vagus nerve and the LPbNe appear to be involved in short­term regulation of food intake, although they participate over different time scales. These data are discussed in terms of the potential importance of the vagal­parabrachial axis in the rapid processing of nutritional information from the upper gastrointestinal tract.

Relevance of the nucleus of the solitary tract, gelatinous part, in learned preferences induced by intragastric nutrient administration.

Food preferences have been investigated in Wistar rats utilizing a learned concurrent flavor preference behavioral procedure. Previous studies have demonstrated that the perivagal administration of neurotoxin capsaicin disrupts the learning of preferences induced by intragastric administration of rewarding nutrients (pre-digested milk). The vagus nerve projects almost exclusively towards the nucleus of the solitary tract (NST), a brain medullary gateway for visceral signals. The objective of this study was to investigate the participation of the lateral portion of the dorsomedial region, the gelatinous subnucleus (SolG), in the learning of a concurrent preference task. Results show that unlike neurologically intact animals, which learn this task correctly, animals lesioned in the gelatinous part of NST manifest a disruption of discrimination learning. Thus, intakes of the flavored stimulus paired with predigested liquid diet and of the flavored stimulus paired with physiological saline were virtually identical. However, SolG- and sham-lesioned groups consumed similar total amounts of both flavors. These findings suggest that SolG, as a relay of the vagus nerve, along with its anatomical projection, the external lateral parabrachial subnucleus (LPBe), may constitute an anatomical axis that is important in the induction of concurrent flavor/side preferences. It also appears to be relevant in other behavioral processes that require rapid processing of information from the upper gastrointestinal tract.

Disruption of re-intake after partial withdrawal of gastric food contents in rats lesioned in the gelatinous part of the nucleus of the solitary tract.

Sensory information from the upper gastrointestinal tract is critical in food intake regulation. Signals from different levels of the digestive system are processed to the brain, among other systems, via the vagus nerve, which mainly projects towards the nucleus of the solitary tract (NST). The objective of this study was to analyze the participation of the gelatinous part (SolG) of the NST in short-term food intake. One-third of the stomach food content was withdrawn at 5 min after the end of a meal, and food was then available ad libitum for different time periods. SolG-lesioned and control animals ingested a similar amount of the initial liquid meal, but the former consumed significantly smaller amounts and failed to compensate for the food deficit, whereas the controls re-ingested virtually the same amount as extracted. These data suggest that the SolG, as in the case of related anatomical structures such as the vagus nerve or external lateral parabrachial subnucleus, may be relevant in particular circumstances that require the rapid processing of vagal-related food intake adjustment associated to the upper gastrointestinal tract.

Chemical afferent vagal axotomy blocks re-intake after partial withdrawal of gastric food contents.

OBJECTIVES: The aim of this study was to investigate the biological process by which animals regulate meal size. An experimental procedure for its study is to examine food re-intake after partial withdrawal of gastric food contents. METHODS: The aim of the present experiments was to investigate the role of vagal afferents in food re-intake after perivagal administration of capsaicin, a neurotoxin that specifically damages weakly myelinated or unmyelinated vagal sensory axons. RESULTS: In experiment 1, capsaicin-treated animals initially consumed higher amounts of food in comparison to controls (in first 24 hours) but their excess intake was compensated for in subsequent daily satiation tests. However, capsaicin treatment impaired the common short-term re-intake behavior observed in control rats after partial removal of gastric food nutrients, and the lesioned animals consumed significantly less food than had been withdrawn after completion of the initial meal; moreover, in this deficit condition, no counteraction was observed in subsequent repeated tests. This behavioral disturbance cannot be attributed to an indirect effect of capsaicin on gastric emptying volume, because the stomach contents were similar in both groups (Experiment 2). DISCUSSION: These findings are discussed in terms of the critical role played by vagal afferents in rapid visceral adjustments related to short-term food intake, as also observed in other gastrointestinal regulatory behaviors that require immediate processing of visceral sensory information.

Satiation and re-intake after partial withdrawal of gastric food contents: A dissociation effect in external lateral parabrachial lesioned rats.

Sensory information from the gastrointestinal system can be transmitted to the brain through the vagus nerve, the intermediate-caudal region of the nucleus of the solitary tract (NST), and various subnuclei of the parabrachial complex, notably the external lateral subnucleus (LPBe). The objective of the present study was to examine the relevance of this subnucleus in satiation and food reintake after gastrointestinal food removal. LPBe-lesioned animals were subjected to a re-intake task following the partial withdrawal of gastric food contents shortly after satiation. Lesioned and control animals ingested a similar amount of the initial liquid meal. However, after withdrawal of one-third of the food consumed, LPBe-lesioned rats were not able to compensate for the deficit created, and their re-intake of food was significantly lower than the amount withdrawn after the satiating meal. In contrast, the food re-intake of control animals was similar to the amount withdrawn. Hence, the LPBe does not appear to be critical in the satiation process under the present experimental conditions. However, the LPBe may be part of a system that is essential in rapid visceral adjustments related to short-term food intake, as also shown in other gastrointestinal regulatory behaviors that require immediate processing of visceral sensory information.

Conditioned place preference but not rewarding self-stimulation after electrical activation of the external lateral parabrachial nucleus.

The objective of this experiment was to examine the rewarding effect of electrical stimulation of the external lateral parabrachial nucleus (LPBe) and of the lateral hypothalamus (LH) in concurrent Conditioned Place Preference (cCPP) and Brain Self-Stimulation Rewarding tasks. As expected, LH-stimulated animals readily learned cCPP tasks and developed self-stimulation behaviours following the rate-frequency procedure. As previously demonstrated, stimulation of the parabrachial complex generated rewarding or aversive behaviours in cCPP procedures. However, stimulation of this subnucleus induced consistent cCPP behaviours but not brain self-stimulation in rewarding LPBe animals. These results are analysed in the context of the different natural and artificial rewarding effects found in the LPBe nucleus.

Consistent rewarding or aversive effects of the electrical stimulation of the lateral parabrachial complex.

Electrical stimulation of the external lateral parabrachial subnucleus (LPBe) may induce rewarding or aversive behaviors in animals subjected to two different learning discrimination tasks. Statistical analysis found no significant differences between the group receiving electrical stimulation of the brain and the non-stimulated control group. However, rewarding or aversive behaviors were consistent and positively correlated between the two discrimination tasks in the stimulated group. Thus, these tests differed in the gustatory stimuli used, in the right/left position of stimulation-associated/non-associated flavors, and in the cage in which experiments were performed. This behavioral consistency and corresponding correlation were not observed in the non-stimulated control group. These results suggest the existence of aversive and reward systems that are differentiated but anatomically very close. Therefore, the activation of aversive or rewarding systems may depend on the precise location of the electrode implanted in the LPBe of each animal.

Effects of intragastric administration of predigested nutrients on food intake, body weight and taste acceptability: potential relevance of the cephalic/neural phase of digestion.

In this study we analyzed the effect of the intragastric administration of partially digested and natural nutrients on subsequent food intake, body weight and flavor acceptability in rats. The results showed that enterally administered natural nutrients reduced the subsequent ingestion of food to a greater degree compared with the same nutrients in partially digested form. This greater reduction does not appear to be due to a higher nutritional effect of the former, because the body weight of both groups of animals was similar. Animals intragastrically administered with partially digested nutrients developed an acceptance response to a previously paired flavored stimulus, in contrast to animals receiving natural nutrients under the same conditions. These results are interpreted in terms of the cephalic phase of digestion and may be relevant to the treatment of clinical symptoms associated with enteral feeding.

Learned flavor preferences induced by intragastric administration of rewarding nutrients: role of capsaicin-sensitive vagal afferent fibers.

Learned flavor preferences can be established after intragastric nutrient administration by two different behavioral procedures, concurrent and sequential. In a concurrent procedure, two flavored stimuli are offered separately but at the same time on a daily basis: one stimulus is paired with the simultaneous intragastric administration of partially digested food and the other with physiological saline. In sequential learning, the two stimuli are presented during alternate sessions. Neural mechanisms underlying these learning modalities have yet to be fully elucidated. The aim of this study was to examine the role of vagal afferent fibers in the visceral processing of rewarding nutrients during concurrent (experiment 1) and sequential (experiment 2) flavor preference learning in Wistar rats. For this purpose, capsaicin, a neurotoxin that destroys slightly myelinated or unmyelinated sensory axons, was applied to the subdiaphragmatic region of the esophagus to selectively damage most of the vagal afferent pathways that originate in the gastrointestinal system. Results showed that capsaicin [1 mg of capsaicin dissolved in 1 ml of vehicle (10% Tween 80 in oil)] blocked acquisition of concurrent but not sequential flavor preference learning. These results are interpreted in terms of a dual neurobiological system involved in processing the rewarding effects of intragastrically administered nutrients. The vagus nerve, specifically capsaicin-sensitive vagal afferent fibers, would only be essential in concurrent flavor preference learning, which requires rapid processing of visceral information.

Learned preferences induced by electrical stimulation of a food-related area of the parabrachial complex: effects of naloxone.

Electrical stimulation of the External Lateral Parabrachial Subnucleus (LPBe), a food-related area, induced behavioral preferences for associated stimuli in a taste discrimination learning task. Although this stimulation appeared to be ineffective to elicit standard lever press self-stimulation, it induced place preference for one of two training compartments of a rectangular maze in which animals (adult male Wistar rats) received concurrent electrical brain stimulation. In subjects that consistently showed a preference behavior in different trials, administration of the opioid antagonist naloxone (4 mg/ml/kg) blocked concurrent learning when the test was made in a new maze but not in the same maze in which animals had learned the task. These results are discussed in terms of the possible participation of the LPBe subnucleus in different natural and artificial brain reward systems.

Capsaicin-sensitive afferent vagal fibers are involved in concurrent taste aversion learning.

Taste aversion learning (TAL) is a type of learning characterized by rejection of a gustatory/flavor stimulus as a consequence of its pairing with visceral discomfort and malaise. TAL can be established in the laboratory by two different behavioral procedures, concurrent or sequential. Neural mechanisms of these learning modalities remain to be elucidated, but several studies have discussed the implication of various anatomical structures, including the vagus nerve. The aim of this study was to examine the role of capsaicin-sensitive vagal afferent fibers in concurrent (Experiment 1) and sequential (Experiment 2) TAL in Wistar rats. Results showed that perivagal administration of capsaicin (1mg of capsaicin dissolved in 1ml of vehicle (10% Tween 80 in oil)) blocked acquisition of concurrent but not sequential TAL. These data support the hypothesis of two different modalities of TAL mediated by distinct neurobiological systems, with vagal nerve participation only being essential in concurrent TAL.

The neural/cephalic phase reflexes in the physiology of nutrition.

The cephalic phase of nutrition refers to a set of food intake-associated autonomic and endocrine responses to the stimulation of sensory systems mainly located in the oropharyngeal cavity. These reactions largely occur in the digestive system, but they have also been observed in other structures. Most published data indicate that cephalic responses are mediated by the efferent component of the vagus nerve, although other neurobiological components and brain centers must be involved. The physiological significance of all of these reactions has yet to be fully elucidated, but when the cephalic phase of digestion is obviated major physiological and behavioral dysfunctions can be observed. This has led numerous authors to propose that their function may be essentially adaptive, preparing the digestive system for the reception, digestion, and absorption of the food. Study of the neural/cephalic phase and the consequences of its absence may have clinical relevance in the setting of artificial nutrition, and may explain the difficulties of providing enteral nutrition to many of the patients that require it.

Concurrent conditioned taste aversion: a learning mechanism based on rapid neural versus flexible humoral processing of visceral noxious substances.

Taste aversion learning (TAL) consists of the avoidance of a taste previously associated with a noxious visceral stimulus. Clinical and experimental studies suggest that this adaptive process can be established by different procedures that imply distinct forms of learning and memory, although the final result is analogous, i.e. avoidance of the gustatory stimulus associated with gastrointestinal discomfort. In fact, a double neurobiological system has been anatomically dissociated and, functionally, may be implicated in nausea and emesis, in food selection, and in neuroimmune interactions. Actually, a dual, parallel, and non-redundant gut-brain system has been proposed that sustain two different TAL modalities, concurrent and sequential. Concurrent TAL requires several trials and is inflexible, requiring simultaneity of the stimuli and the participation of the vagus nerve. In contrast, sequential TAL can be acquired in one trial and is flexible, permits long inter-stimulus delays, and is independent of vagal pathways. These two TAL modalities are analyzed in the light of the recent proposal that different acquisition processes are sustained by distinct cerebral systems.

Lesions of the lateral parabrachial area block the aversive component and induced-flavor preference for the delayed intragastric administration of nutrients in rats: effects on subsequent food and water intake.

The aim of this study was to examine the function of the lateral parabrachial area (LPB) in relation to the intragastric administration of nutrients. The consumption of flavors associated with intragastric nutrient administration and the subsequent food and water intake were measured in rats with lesions in the LPB. The results showed that bilateral LPB lesions prevented development of aversions and induced flavor preference when there was a delay between the presentation of a flavor and the intragastric administration of nutrients. However, these lesions did not disrupt development of the aversive process when there was no delay between the presentations. Likewise, the LPB lesions increased subsequent food intake when there was a delay but not when there was no delay between the presentations. In contrast, the water intake was reduced in both situations. These results are interpreted in terms of a dual visceral system for processing the intragastric effects of foods.

Effects of perivagal administration of capsaicin on food intake in animals after noxious gastric surgery.

Previous studies have shown that the perivagal administration of capsaicin induces greater food intake vs. controls at 24 h after the surgery but a similar intake to that of controls at 48 h. The present study aimed to determine whether the nutritive effect observed after perivagal capsaicin administration is due to the interruption of noxious vagal fibers in rats. For this purpose, postsurgical food intake was analyzed in control and capsaicin-treated animals with (Experiment 2) and without (Experiment 1) noxious lesions in the gastric wall. The results of both experiments showed that the food intake of capsaicin-treated animals was greater vs. control animals at 24 h but not at 48 h after the surgery (p<0.025), as previously demonstrated. However, the food intake of the capsaicin-treated lesion animals in Experiment 2, although still greater than that of the control group, was significantly less than the intake of the capsaicin-treated animals in Experiment 1 (p<0.01). Therefore, it appears unlikely that the demonstrated effect is produced by lesion to noxious vagal fibers destroyed by the capsaicin. On the contrary, it is more likely that the vagal afferent pathways are those related to short-term nutrition.

Effects of perivagal administration of capsaicin on post-surgical food intake.

The vagus nerve has been related to the short-term control of food intake. This involvement has previously been explored by examining the food intake of animals after recovery from a vagotomy or immediately after the intervention, among other methods. In the present work, a study was conducted on the impact of the perivagal application of capsaicin (a specific neurotoxic treatment that destroys most of the vagal afferent pathways) on the intake of water and solid (experiment 1) or liquid (experiment 2) food presented after the surgery The results of experiment 1 showed that lesioned animals consume significantly larger amounts of food and water compared with controls at 6, 12, and 24 h (but not at 48 or 72 h) after the surgical intervention. Likewise, experiment 2 revealed a greater intake of liquid food by capsaicin-treated animals at the first post-surgical sessions. These data are discussed in terms of the role played by vagal afferent fibers in the control of short-term food intake.