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Vasoactive intestinal peptide (VIP), a neuromodulator present in the hypothalamus, plays an important role in the regulation of food intake. Paraventricular nucleus of the hypothalamus (PVN) is involved in ingestive responses and regulates the nitric oxide (NO) pathway. The main objectives of this study were to investigate metabolic changes established after different doses and times of VIP microinjection on the PVN, and the effect of VIP microinjection on the PVN on food intake and the role of NO in this control. In anesthetized rats, increased blood plasma glucose and insulin levels were observed following the doses of 40 and 80 ng/g of body weight. At the dose of 40 ng/g, VIP promoted hyperglycemia and hyperinsulinemia 5, 10, and 30 min after microinjection, and increased free fatty acids and total lipids plasma levels after 5 min, and triglycerides after 10 min. In awake animals, once again, VIP administration increased plasmatic levels of glucose, free fatty acids, corticosterone, and insulin 10 min after the microinjection. Moreover, VIP promoted hypophagia in the morning and night periods, and L-arginine (L-Arg) and monosodium glutamate (MSG) or a combination of both attenuated VIP-induced reduction on food intake. In addition, nitrate concentration in the PVN was decreased after VIP microinjection. Our data show that the PVN participates in the anorexigenic and metabolic effects of VIP, and that VIP-induced hypophagia is likely mediated by reduction of NO., Competing Interests: Conflict of interest The authors report no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The effect of neonatal treatment with monosodium L-glutamate (MSG) on the dopaminergic systems of the medial basal hypothalamus has been investigated using tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) immunocytochemistry. Changes in plasma levels of prolactin (PRL) and alpha-melanocyte-stimulating hormone (MSH) have also been determined in intact and in MSG-treated rats after inhibition of TH by alpha-methyl-p-tyrosine (alpha-MpT) or without inhibition of enzyme activity. Monosodium glutamate resulted in a 40% reduction in the number of TH immunopositive tuberoinfundibular neurons, but no change in the number of AADC-positive tuberoinfundibular nerve cells, indicating that this reduction has occurred mainly in TH-positive but AADC-negative elements, i.e., in L-DOPA-ergic neurons. In contrast, MSG did not cause changes in the number of TH and AADC immunoreactive neurons of the periventriculohypophysial and tuberohypophysial dopaminergic systems, and it did not influence basal plasma PRL levels. alpha-methyl-p-tyrosine has increased plasma PRL concentrations in both control and MSG-treated rats of both sexes, but significantly higher responses were detected in females. None of the treatments had any effect on plasma MSH level. These findings suggest that MSG affects primarily L-DOPA-ergic neurons located in the ventrolateral part of the arcuate nucleus, but not dopaminergic neurons situated in the dorsomedial part of the arcuate nucleus; neither PRL nor MSH secretion is altered by MSG; a significant sex difference exists in the pituitary PRL response to inhibition of TH, and this response is not affected by MSG.

Neonatal monosodium glutamate (MSG)-treated rats were used in this study to answer two questions: (1) whether or not the dopamine-responsive dorsomedial arcuate (dm-ARN) neurons are tuberoinfundibular dopaminergic (TIDA) neurons, and (2) whether or not the remaining TIDA neurons in MSG-treated rats are functioning normally. MSG (4 mg/g b. wt., subcutaneously [s.c.]) or saline was given to neonatal Sprague-Dawley rats on days 1, 3, 5, 7, and 9 after birth. The female rats were ovariectomized at 50 days of age and treated with estrogen for 1 week before they were used between 65-90 days of age. The tyrosine hydroxylase-immunoreactive (TH-ir) neurons located in the dm and ventrolateral (vl) parts of the ARN were significantly reduced in MSG-treated rats, as determined by immunohistochemical method. Some TH-ir cells, however, were visible along the border of the third ventricle. Using single-unit recording in brain slices, we found that dopamine inhibited significantly fewer percentage of dm-ARN neurons in MSG-treated (28.2%, n = 39) than in saline-treated rats (73.3%, n = 15). In contrast, bombesin exhibited similar effects (over 70% excitation) in both groups. Using neurochemical means, neonatal MSG treatment produced significant decreases of both 3,4-dihydroxyphenylacetic acid and dopamine levels, but not their ratios, in the median eminence. Moreover, the diurnal change of TIDA neuronal activity persisted in the MSG-treated rats; so did the estrogen-induced afternoon prolactin surge. All these results indicate that neonatal MSG-treatment reduced the number and altered the location of TIDA and dopamine-responsive dm-ARN neurons. The remaining TIDA neurons seemed to be able to maintain their basal activities and diurnal rhythm.

Glutamate administration in neonatal rats causes reversible changes in blood-brain barrier (BBB) permeability and known neurotoxic lesions. This study was aimed to evaluate whether glutamate administered to neonatal rats influences properties of the developing BBB with consequences on adult BBB function. The vulnerability of the BBB was examined after short-lasting stress exposure by measurement of plasma albumin extravasation using immunoelectrophoresis. In control rats, 30 min of immobilization stress resulted in increased endogenous albumin extravasation in the hypothalamus, hippocampus, brain stem and cerebellum, but not in the cortex and striatum. Basal levels of albumin in adult glutamate-treated rats (4 mg monosodium glutamate/g BW, IP, five times during neonatal period) were significantly lower in the hypothalamus compared to that in controls. Stress-induced increase in albumin levels was lower in the brain stem, higher in the hypothalamus, and similar in other brain regions studied in glutamate-treated rats in comparison with controls. It is concluded that short-lasting immobilization stress increased BBB permeability in some but not all brain regions studied. Glutamate treatment of neonatal rats resulted in low basal albumin levels in the hypothalamus but did not exert a pronounced influence on adult BBB function. BBB vulnerability in glutamate-treated rats during stress exposure was increased in the hypothalamus and decreased in the brain stem.

The RNA content of the ventromedial hypothalamus (VMH), the lateral hypothalamic area (LHA), and the cortical neurons of male and female rats, neonatally treated with monosodium glutamate (MSG), were investigated. MSG (2 g/kg b.wt.) was injected subcutaneously to male and female rat pups daily for 5 days after birth. At 12 weeks of age a significant decrease of RNA content in the VMH cells and significantly increased body fat in neonatally MSG-treated animals were found. Correlation of these data showed a significant negative correlation between the body fat content and the RNA content in VMH neurons. The results a) confirm a closed relationship between the body fat content and the functional activity of VMH, b) indicate that obesity of neonatally MSG-treated animals should be due to decreased functional activity of the VMH cells.

The mechanisms controlling central and systemic oxytocin (OT) release were examined using in vivo microdialysis of the paraventricular (PVN) region. Dialysate and plasma samples were collected from conscious male rats and stimuli were administered via the dialysate fluid. Characterization studies showed that microdialysis was a viable technique for the study of peptide secretion in the conscious animal. OT was consistently detected in the PVN dialysate and a partially purified extract crossreacted in parallel fashion with the synthetic peptide. In vitro studies showed that peptide recovery was positively correlated with the pore size of the dialysis membrane and that there was an inverse relationship between flow rate and recovery. Hypertonic saline administered centrally caused an increase in dialysate and plasma oxytocin while the intravenous injection affected only plasma oxytocin. The excitatory amino acid, glutamate (0.05-0.5 M), caused an increase in plasma, but not dialysate oxytocin, while depolarization with potassium chloride (0.05-0.15 M) had no significant effects. Histological examination showed that the dialysis probe was located in the rostral, lateral PVN. Our results show that in vivo microdialysis provides a method for the delivery of drugs into specific brain regions as well as a useful technique for the evaluation of in vivo neuropeptide release.

Effects of umami taste stimulation with monosodium glutamate (MSG) on the efferent discharges in the pancreatic, gastric and hepatic branch of the vagus nerve were observed in the anesthetized rat, in comparison with those of sweet and salty taste stimulation. Umami taste stimulation with 2.8% MSG solution caused an enhancement of vagal activities in pancreatic, gastric and hepatic branches. Sweet taste stimulation with 5% glucose or 10% sucrose increased efferent activity of hepatic and pancreatic branches and inhibited in gastric branch of the vagus nerve. Salty taste stimulation with 5% NaCl resulted in an increase in vagal gastric nerve activity and a decrease in that of vagal pancreatic and hepatic nerve; however, weak salty taste stimulation with 0.9% NaCl solution caused no remarkable change in efferent activity. It was assumed that umami taste stimulation, strong salty taste stimulation and sweet taste stimulation revealed different patterns of vagal responses which play some role on different anticipatory changes in hepatic, pancreatic and gastric functions following ingestion of food with different taste.

Behavioural effects of carbachol given into the hypothalamic/preoptic area have been demonstrated but there is a paucity of information about the response of single neurons to carbachol. The aim of the present study was to determine the response of spontaneously firing neurons in the rat hypothalamic/preoptic area to application of carbachol by iontophoresis or by pressure injection in a dose and volume comparable with that used in behavioural studies. Extracellular single unit recordings showed a significant decrease in mean firing rate in 82% of neurons responding to iontophoretic carbachol and in 75.5% of neurons responding to carbachol injected about 600 microns away. An increase in firing rate occurred in only 15 and 17.6% of neurons, respectively. Application of saline did not alter the mean firing rate while application of glutamate into the same areas or ejection into the vicinity of the same neurons caused an increase in mean firing rate in 94% of responding neurons. The results indicate that a decrease in mean firing rate is the predominant neuronal response to carbachol in the anteromedial hypothalamic/preoptic area of the rat and we suggest that this decrease may be associated with behavioural responses to carbachol.

The rodent superior colliculus mediates a wide range of physiological and behavioural responses to sudden stimuli, including desynchronisation of the cortical electroencephalogram (EEG). To investigate how this desynchronisation is produced, one of two powerful excitatory agents, sodium L-glutamate (200 nl, 10 nmol) or bicuculline methiodide (200 nl, 40 pmol), was injected into the dorsal midbrain of sleeping rats. Microinjections at sites widely distributed throughout all layers of the superior colliculus were able to desynchronise the cortical EEG. i) In the superficial layers, bicuculline was effective at more sites than glutamate, whereas the reverse was true for the deep layers. ii) At some sites EEG desynchronisation occurred together with the defensive or orienting movements that are obtained from collicular stimulation in awake animals. At other sites cortical arousal occurred without such movements. iii) Comparison with a previous study suggested that urethane selectively blocks cortical arousal to glutamate injections in the superficial and intermediate grey layers. This evidence suggests that multiple collicular output pathways can desynchronise the cortical EEG, perhaps reflecting multiple functions for EEG desynchronisation.

Neuropeptide Y (NPY) concentration was determined by radioimmunoassay in selected hypothalamic regions microdissected from fresh brain slices of rats treated neonatally with monosodium glutamate (MSG). Fourteen weeks after MSG treatment, significant decreases in NPY concentration were found in the paraventricular nucleus (PVN) and arcuate nucleus (ARH), while there was no appreciable change in the ventromedial nucleus (VMH) and lateral area (LH). The decrease in NPY in the ARH-PVN system may contribute to the endocrine and metabolic disturbances seen in MSG-treated animals.

Neonatal administration of monosodium glutamate (MSG) produces necrosis of circumventricular structures, including perikarya in the medial-basal hypothalamus that contain beta-endorphin (BEND) and met-enkephalin. Since neonatal MSG treatment alters morphine analgesia, the present study examined neonatal MSG effects upon opioid analgesia observed following either BEND or d-ala d-leu enkephalin (DADL). Rats treated with either MSG or vehicle over the first ten post-natal days, were surgically prepared with a lateral ventricle cannula at 100 days of age. Respective groups received central injections of either BEND (0, 0.1, 0.5 or 1.0 microgram) or DADL (0, 4, 20 or 40 micrograms), and jump thresholds were assessed 15, 30, 45 and 60 min thereafter. Following testing, selected MSG-treated and control animals were prepared for BEND immunocytochemistry. While the magnitude, duration and sensitivity of BEND analgesia on the jump test failed to differ between groups, MSG-treated rats displayed a 10-fold leftward shift in sensitivity and a 200-300% increase in the magnitude of DADL analgesia. Immunocytochemical analysis indicated that MSG treatment depleted perikarya in the medial-basal hypothalamus, periventricular thalamic fibers and periaqueductal gray terminal fields that contained BEND. The differential effects of MSG treatment upon opiate and opioid analgesia are discussed in terms of possible alterations in opiate receptor subpopulations.

Neonatal treatment with monosodium glutamate (MSG) induces severe neurochemical damage to several brain regions, and these lesions are expressed in adult life by a variety of endocrine and behavioral abnormalities. The present study analyzes the extent of the neurochemical damage to several monoaminergic systems by evaluating the changes in norepinephrine (NE), dopamine (DA), and 5-hydroxytryptamine (5-HT) metabolism induced by the neurotoxin in several discrete hypothalamic loci. Moreover, the study also evaluated the ability of MSG-treated rats to respond to acute ether stress, by measuring the release of ACTH and prolactin induced by ether and correlating those changes with the alterations in monoamine metabolism in the arcuate (AN), dorsomedial (DMN), and suprachiasmatic (SCN) nuclei and in the median eminence (ME). The results indicate that MSG treatment induces marked changes in monoamine metabolism in several of the regions examined. The metabolite of DA, dihydroxyphenylacetic acid, was markedly depressed in the AN, SCN, and DMN. NE metabolism was also significantly lower in the AN of MSG-treated animals. 5-HT metabolism was also altered by MSG treatment, with significant decrements recorded in the SCN, DMN, and AN. Both control and MSG-treated rats showed highly significant increments in ACTH and PRL release 5 and 15 min after exposure to ether vapors. The only quantitative difference between the two groups was a smaller increment in ACTH levels 5 min after ether in the MSG group. Ether stress increased DA metabolism in the AN, NE metabolism in the AN and DMN, and 5-HT metabolism in the SCN in control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Mice treated neonatally with MSG (4 mg/g) were compared to saline-injected controls on a number of neurochemical parameters of brainstem noradrenergic activity. MSG treatment resulted in an attenuation of brainstem norepinephrine (NE) decline after alpha-methyl-p-tyrosine administration. Neonatal MSG administration did not result in alterations in the steady state levels of brainstem NE or MOPEG. The synthesis of NE was slightly increased in the pons-medulla of MSG-treated mice as indexed by pargyline-induced NE accumulation. NE release, however, appeared diminished as reflected by a significant (p less than 0.05) decrease in the ratio of normetanephrine to NE found in the pons-medulla of MSG-treated mice given pargyline. The results suggest that MSG-induced damage to the arcuate nucleus produces selective alterations in brainstem NE systems. These alterations may reflect the toxic action of MSG on the opiomelanocortin neurons of the arcuate nucleus or other descending systems that are damaged by MSG. The loss of the descending opiomelanocortin input to the brainstem could result in these types of neurochemical consequences since the pharmacologic action of opiate drugs results in a selective enhancement of brainstem NE turnover in rodents.

Stimulation of the rat superior colliculus can produce either orienting or defensive movements, which if elicited by natural stimuli would be accompanied by cardiovascular changes. To assess whether cardiovascular changes might also be mediated by the superior colliculus, blood pressure and heart rate were measured in Saffan-anaesthetised rats while the dorsal midbrain was systematically explored with electrical and chemical stimulation. Electrical stimulation (10 sec trains of 0.3 msec 100 Hz cathodal pulses, 50 microA) within the superficial and intermediate layers of the rostral superior colliculus transiently lowered blood pressure without affecting heart rate. In contrast sites within the deep layers, and in adjacent periaqueductal grey and midbrain tegmentum, gave pressor responses accompanied by a variety of heart-rate changes, that usually included a period of bradycardia. A roughly similar distribution was obtained with the cell-stimulant bicuculline (200 or 500 nl, 490 microM), though sodium L-glutamate (200 nl, 0.05 or 1.0 M) was ineffective. These results suggest that (a) cardiovascular responses can be produced by stimulation of the rat superior colliculus; (b) their nature depends on the location of the stimulation; and (c) they may be mediated in part by cells differentially sensitive to glutamate and to bicuculline. In addition, in some animals respiratory responses were measured stethographically. Short-latency increases in thoracic girth, often accompanied by increases in respiratory rate and depth, were elicited by electrical stimulation from 61% of the collicular sites examined, and by microinjection of glutamate from 56% of collicular sites. These data suggest that (a) cells within the superior colliculus are capable of influencing respiration; (b) given the widespread distribution of responsive sites within the superior colliculus, the respiratory changes may be preparatory for both approach and defensive movements; (c) the collicular cells that affect respiration may be different from those that influence blood pressure, because the latter are relatively insensitive to microinjection of glutamate.

Monosodium Glutamate (MSG), known to induce neuronal cell degeneration of the arcuate nucleus of the hypothalamus, was subcutaneously injected (4 mg/g body wt.) at postnatal days 1 to 5 or 1 to 10 in female rats. Hypophysectomy was performed at 45-60 days of age. Sleep parameters were continuously recorded for at least 7 days. Results indicated that hypophysectomized (HYPX) NaCl-treated rats showed an increase of Slow Wave Sleep (SWS) (+29.6%) and a decrease of Paradoxical Sleep (PS) (-36.7%) durations. In MSG-treated rats, hypophysectomy did not alter SWS durations but it increased PS durations as MSG dosing increased. It was concluded that arcuate nucleus neurons seemed to be not critically involved in sleep production mechanisms.