Filomena Molina

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.

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.

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.

Bilateral lesions in the cerebellar interpositus-dentate region impair taste aversion learning in rats

Taste Aversion Learning (TAL) has been induced through two different behavioral procedures: a short-term o concurrent (two-daily flavors) and a long-term (one-daily flavor) procedure. For the first, two gustatory/olfactory stimuli are presented separately but at the same time on a daily basis. One of the flavors is paired with simultaneous intragastric administration of hypertonic NaCl and the other is paired with physiological saline. In the long-term procedure, the two stimuli are presented on alternate days, one of them followed by intragastric injection of the aversive stimulus, and the other by saline. The subjects for both types of tests were animals that had been lesioned in the interpositus-dentate region of the cerebellum. The experiments show that the lesions disrupt short-term TAL, but have no effect on long-term TAL. The results are discussed in terms of the role of the cerebellum in relation to TAL and the different anatomical substrates of both learning modalities.

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.

The role of the lateral parabrachial nuclei in concurrent and sequential taste aversion learning in rats.

Abstract. The purpose of this study was to examine the role of the external lateral parabrachial subnucleus (PBNLe) in two different taste aversion learning (TAL) procedures. For the first, short-term (concurrent) TAL, two different-flavored stimuli were presented at the same time, one associated with simultaneous intragastric administration of an aversive product, hypertonic NaCl, and the other with saline. In the second, long-term (sequential/delayed) TAL, each gustatory stimulus was presented every other day and the intragastric products LiCl and saline were administered after a 15-min delay. Electrolytic lesions in the PBNLe blocked acquisition of concurrent TAL, in which the vagal visceral information is critical. But the same lesions failed to interrupt sequential TAL. This result was independent of the order in which the two tasks (concurrent and sequential) were presented. However, as found by other authors, the latter type of learning was impaired in the presence of larger lesions in this same area. This supports the existence of sensory information needed to establish sequential TAL in other subnuclei of the parabrachial complex. The results of these experiments suggest that the different modalities of TAL are anatomically specific.

The functional relevance of medial parabrachial nucleus in intragastric sodium chloride-induced short-term (concurrent) aversion learning.

The functional meaning of the visceral information processing in the medial parabrachial nucleus (PBNm) was analyzed in this study through a short-term aversion learning task. In this short-term task the animals (Wistar rats) had to learn to discriminate between two different gustatory-olfactory stimuli presented simultaneously (two graduated burettes); one of the stimuli was associated with the concurrent intragastric administration of an aversive chemical agent (hypertonic NaCl) and the other stimulus was paired with no injection. In the first experiment, the PBNm-lesioned animals are unable to learn the task using gustatory stimuli (saccharin and quinine) that surpassed the detection threshold of parabrachial-lesioned rats. Moreover, in a second experiment, the PBNm-lesioned animals were unable to learn the task when there was no initial preference for either of the gustatory-olfactory stimuli presented (strawberry or coconut). However, this short-term task is learned by lateral parabrachial nucleus (PBNl) lesioned animals. The possibility that the PBNm and the PBNl are involved in distinct mechanisms of visceral processing is discussed.

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.

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.