María A. Zafra

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.

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.

The role of the external lateral parabrachial subnucleus in flavor preferences induced by predigested food administered intragastrically.

A study was undertaken of the role of the external lateral parabrachial subnucleus (PBNLe) in flavor preferences induced by the intragastric administration of predigested/cephalic food. These preferences were developed using two different learning procedures, concurrent and sequential. In the concurrent procedure, two different-flavored stimuli were presented at the same time: one stimulus was paired with the simultaneous intragastric administration of partially digested food and the other with physiological saline. In the sequential learning procedure, the two stimuli were presented at alternate sessions. The results showed that PBNLe lesions blocked acquisition of concurrent learning but had no effect on the sequential procedure. In the latter case, both lesioned and control animals showed a strong preference for the gustatory stimulus paired with partially digested food. These results are interpreted in terms of a dual neurobiological system involved in the rewarding effects of visceral signals.

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.

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.

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.

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.

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

Abstract 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.

Rewarding effects of electrical stimulation of the insular cortex: decayed effectiveness after repeated tests and subsequent increase in vertical behavioral activity and conditioned place aversion after naloxone administration.

The insular cortex has been associated with various aversive and rewarding sensory, regulatory, and learning processes. The objective of this study was to examine the characteristics of the reinforcement induced by electrical stimulation of this brain area in rats. Results obtained confirm that electrical stimulation of the insular cortex may induce conditioned place and flavor preferences but the learning acquired is not transferred in a reversal test. Unexpectedly, they also demonstrate that this rewarding effect diminishes after repeated tests. In follow-up experiments, locomotor activity tests revealed an increased number of rearings (a sensitization index) in stimulated animals. Furthermore, in these same animals, administration of low doses of naloxone, an opiate antagonist, developed place aversion toward the maze compartment for which the animals had previously shown preference. These results are interpreted in relation to the effects induced by the repeated administration of natural and artificial rewarding stimuli.

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.