Carlos V. Grijalva

Functional correlations between lateral hypothalamic glucose-sensitive neurons and hepatic portal glucose-sensitive units in rat

The effects of glucose injection into the hepatic portal vein on neural activity of the lateral hypothalamic area (LHA) were studied in rats. A majority of identified glucose-sensitive neurons in the LHA were inhibited by portal injection of glucose. This was found to be mediated through the alpha-noradrenergic pathways. Most of the glucose-insensitive neurons did not respond to the same procedure. Portal injection of hypertonic saline increased neural activity of some glucose-insensitive neurons but no glucose-sensitive neurons responded. Convergence of hepatic vagal afferent glucose-sensitive units on LHA glucose-sensitive neurons was clarified by this study.

Flavor-illness aversions: The role of the amygdala in the acquisition of taste-potentiated odor aversions

In the present experiments the role of the amygdaloid complex and its specific nuclei were tested in the conditioning of taste potentiated odor aversions. In the first experiment two groups of rats were given either large electrolytic lesions in the amygdala (AMX) or sham operations (SH). Postoperatively, these rats were trained to avoid either a taste, an odor, or a taste-odor compound using LiCl illness. Subsequent tests with odor and taste alone showed that the SH group developed strong taste and odor aversions; however, the AMX group failed to display either an odor or taste aversion. In the second experiment, another four groups of rats received either lesions in the medial and basomedial nuclei (M), central nuclei (C), lateral and basolateral (L), or sham operations (SH). The results from postoperative conditioning showed that all groups had strong taste and odor aversions, except group L which displayed a significant disruption of odor aversion learning. In conclusion, these data indicate that the amygdala is involved in the acquisition of taste, odor and potentiated odor aversions learning. Moreover, it is demonstrated that the lateral and/or basolateral nuclei are particularly involved in the development of potentiated odor aversions learning.

The Role of the Hypothalamus and Dorsal Vagal Complex in Gastrointestinal Function and Pathophysiology

A foregone conclusion is that central neural and endocrine control of gastrointestinal functions is based on a complex array of interconnecting brain structures, neurochemical systems, and hormonal modulators. As might be expected, a considerable degree of redundancy is seen not only in the manner in which certain brain structures appear to participate in the regulation of GI functions, but also in the extent to which certain neurotransmitters or brain-gut peptides, when injected centrally, alter these functions. Despite the seemingly ambiguous nature of brain-gut interactions, a picture is beginning to unfold that suggests that GI properties are based on certain reflexes (e.g., vago-vagal). These reflexes, in turn, appear to be influenced by brain structures in a hierarchical manner, not all that dissimilar to the system described by Papez and expanded on by MacLean several years ago. For example, the perceptual or cognitive aspects of both external and internal stimuli are monitored at various brain levels, but obviously higher cortical processes are intimately involved. Aversive events provide sensory information, which is integrated primarily by the limbic system (e.g., amygdala) and translated into the expression of emotional behavior and associated autonomic response patterns. Various hypothalamic structures, in turn, appear most strongly to influence physiological changes associated with aversive events by virtue of the direct connections to the autonomic and endocrine systems. Ultimately, the visceral outcome can be seen as being based on the integrated convergence of information from cortical, limbic, and hypothalamic structures onto medullary nerve nuclei as well as other efferent systems. With respect to animal models of neurogenic or stress ulcer, activity of the dorsal vagal complex and vagal efferents appears to be the final common pathway for pathologic changes in the gut.

Contrasting effects of centromedial and basolateral amygdaloid lesions on stress-related responses in the rat

The effects of lesions in the centromedial and basolateral amygdala were examined using three different tests sensitive to the following stress-related responses: exploratory behavior, pain reactivity, and immune responses. The most clear-cut results were found with exploratory behavior. Rats with lesions of the centromedial amygdala tended to explore a radial-arm maze more quickly and entered more novel arms of the maze than controls. Those with lesions of the basolateral amygdala were generally too hesitant to explore at all. No significant differences were found between groups on measurements of natural killer cell activity. In tests of pain perception, rats in the control group displayed an analgesic response on the hot plate following an injection of the anxiogenic drug, RO 15-1788, whereas rats with centromedial lesions tended to exhibit a blunted response. These findings provide modest support for the view that the central and lateral regions of the amygdala play complementary roles in aversively motivated behaviors and in stress-related response patterns.

Amygdaloid lesions attenuate neurogenic gastric mucosal erosions but do not alter gastric secretory changes induced by intracisternal bombesin.

Bilateral lesions of the lateral hypothalamus in rats produce glandular gastric mucosal damage. The results of the first experiment demonstrated that the severity of the neurogenic gastric erosions is attenuated by prior lesions of the centromedial amygdala. In a second experiment it was shown that fasting gastric acidity is significantly reduced following chronic amygdaloid lesions and this may be the mechanism involved in the protective nature of the amygdaloid lesions against gastric mucosal damage. In addition, it was found that gastric secretory changes induced by intracisternal injection of bombesin are unaffected by amygdaloid damage. The present results are consistent with the view that the centromedial amygdaloid region may influence gastric functions by modulating the activity of the preoptic-anterolateral hypothalamic areas or by directly influencing lower brain stem autonomic control areas.

Taste reactivity in rats following lesions of the zona incerta or amygdala

Abstract Rats with amygdala lesions (n=12) and rats with zona incerta lesions (n=12) were compared to normal rats (n=12) in their response to various taste stimuli. Five concentrations each of sucrose, sodium chloride, quinine hydrochooride, and hydrochloric acid were presented to all animals in single bottle tests during a schedule of restricted fluid access. Results indicated that both groups of rats with lesions had significantly lower baseline water consumption than normal rats. Using taste consumption measures expressed as a percent of water baseline, it was found that zona incerta lesions did not significantly alter normal taste reactivity. Animals with zona incerta lesions did fail to show normal habituation to a 0.0001 M quinine solution over repeated presentations. Lesions of the amygdala resulted in an increase in consumption of the acid solutions; consumption of sucrose, quinine, and sodium chloride was normal across concentrations. Amygdala damaged rats failed to show normal neophobia when first presented with the 0.0001 M quinine solution. It was concluded that taste response functions of rats with lesions of the zona incerta or amygdala remain essentially normal following surgery but that subtle changes in reactivity do occur, particularly with regard to neophobia.

Body Temperature and Wheel Running Predict Survival Times in Rats Exposed to Activity-Stress

The relationship between restricted feeding, core body temperature (Tb), wheel running, survival, and gastric erosion formation was examined in female rats exposed to activity-stress. Core body temperature and gross motor activity were telemetrically monitored in four groups of rats that had free access to running wheels and in one group that was not allowed to run on the wheels. Twenty-four hours prior to the onset of hypothermia and predicted mortality, different groups were left undisturbed, warmed with a heat lamp, denied access to running wheels, or euthanized. Length of survival in wheel-running rats varied from 2 to 12 days. During the first day of food deprivation, premorbid changes in the variability of Tb during the diurnal period and the mean number of wheel revolutions during the nocturnal period were strongly predictive of length of survival. Warming rats with a heat lamp or preventing rats from ever running on the wheel increased the length of survival and attenuated gastric erosion formation. Only rats that were warmed had a greater likelihood of survival. Gastric pathology was also reduced in rats that were euthanized prior to becoming moribund. Rats that were left undisturbed or locked from the running wheel over the last 24 h of testing became moribund and had extensive gastric mucosal damage. These results indicate that thermoregulatory disturbances induced by restricted feeding and not wheel running alone are critical in determining survival and the degree of gastric mucosal injury in rats exposed to activity-stress. Results further suggest that predisposing factors may put some rats at risk for the development of activity-stress-induced mortality.

Stimulation of gastric secretion by acute lateral hypothalamic lesions and its reversal by intracisternal injection of bombesin

Lateral hypothalamic (LH) but not lateral thalamic (LT) electrolytic lesions markedly increased gastric secretion (volume and acidity) in rats within 2 h of production of the lesions and pylorus ligation. Intracisternal injection of bombesin inhibited gastric secretion (volume and acidity) and reduced to control levels the enhanced acid output produced by the LH lesions. These data demonstrate that acute LH lesions stimulate gastric secretion, and that bombesin exerts a potent gastric antisecretory influence, probably through interaction with LH-related stimulatory pathways.

Alterations in blood glucose, insulin, and free fatty acids following lateral hypothalamic lesions or parasagittal knife cuts

Abstract The effects of lateral hypothalamic (LH) lesions or parasagittal knife cuts placed lateral to the LH on levels of serum glucose, insulin and lipids were examined in 3 separate experiments. The first experiment showed that 24 hr after surgery, free fatty acid (FFA) levels were significantly lower in the knife cut group than in the groups given LH lesions or control operations. However, blood glucose was higher in both the knife cut group and LH lesion group relative to controls. In a second experiment, groups of rats given LH lesions, knife cuts or control operations were allowed 25 days postoperative recovery. The LH lesion group had higher FFA levels, lower triglyceride, insulin, and glucose levels than the knife-cut or normal weight control group. However, FFA, triglyceride and insulin levels for the LH group did not differ from its weight-paired control group. The third experiment demonstrated that LH lesions and knife cuts altered FFA mobilization in response to 2-DG, however, only knife cuts altered the hyperglycemia induced by 2-DG. This suggests that the parasagittal knife cuts uniquely interrupt the sympathetic activation of the adrenal medulla. The results of the present study indicate that although LH lesions and parasagittal knife cuts induce similar patterns of ingestive disorders, the autonomic and metabolic alterations resulting from these two surgical procedures are quite different.

Gastric Mucosal Damage in Rats Induced by Lateral Hypothalamic Lesions: Protection by Propantheline, Cimetidine, and Vagotomy

Summary Experiment 1 demonstrated that gastric mucosal damage in rats induced by lateral hypothalamic (LH) lesions could be significantly reduced by antisecretory doses of propantheline, cimetidine, and by vagotomy, however, only propantheline also prevented hypersalivation and chromodacryorrhea. These results indicate that a primary effect of LH lesions is to produce an abrupt increase in parasym-pathetic activity. Experiment 2 showed that gastric mucosal barrier functions were altered by LH lesions even before visible defects of the mucosa were present. It is suggested that an increase in permeability of the gastric mucosa may play an important role in the pathogenesis of gastric ulceration induced by hypothalamic damage.