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Influence of female odors on lateral hypothalamus in the male rat. Semiquantitative deoxyglucose analysis.

The uptake of 14C deoxyglucose (2DG) has been studied in various hypothalamic and limbic structures of male rats exposed to female odors. Uptake differences were visualized by image processing and quantified by measurement of optical density ratios. With respect to the control group, an increase in uptake was observed in the lateral hypothalamic area (LHA), not only in the olfactory bundle, but also, and more obviously, in the parafornical part. This 2DG response is not a result of an odor-induced general motor activation, although it seems to depend on the behavioral reaction of the animal towards the odor. A similar correspondence was not observed for the 2DG response to odor in the ventromedial hypothalamus. Observations in the medial preoptic area, in the corticomedial amygdala, in the lateral septum, or in the dorsomedial hypothalamus did not reveal any significant change in 2DG uptake.

Animals↗

Circadian changes in the RNA content of rat hypothalamic nuclei in relation to food intake.

The ribonucleic acid (RNA) and protein content of the ventromedial hypothalamic nuclei (VMH), the lateral hypothalamic areas (LHA) and the cortex (C) of adult male Wistar rats followed free access to food and water were determined at 6-hour intervals (at 6.00, 12.00, 18.00 and 24.00 h); the RNA and protein content of the suprachiasmatic nuclei (SCN) were determined at 12.00 and 24.00 h. The RNA content of the VMH, LHA and SCN differed at various intervals; in the cortex it did not alter significantly. The highest RNA concentration in the VMH was recorded at 18.00 h and in the LHA at 24.00 h, after which, in both areas, it fell. The lowest RNA content in the LHA and the VMH was found at 12.00 h. In the SCN, the RNA concentration at 24.00 h was significantly higher than at 12.00 h. The protein content did not alter significantly during the circadian cycle in any of the structures examined.

Animals↗

Adrenal medullary secretion in response to diencephalic stimulation in the rat.

The effect of diencephalic stimulation on adrenal medullary secretion was investigated in pentobarbital-anesthetized rats. Adrenal secretions of epinephrine and norepinephrine were evaluated by collection and fluorometric analyses of adrenal venous blood samples. A significant increase in epinephrine secretion was produced by stimulation of the dorsomedial, ventromedial and lateral hypothalamic areas and the posterior regions of the thalamus. Most of the positive responsive areas in the diencephalon were localized near the dorsomedial hypothalamic nucleus. In contrast, a significant decrease in epinephrine secretion with or without a significant decrease in norepinephrine secretion was observed following stimulation of the preoptic area and lateral hypothalamic region and a significant decrease in norepinephrine secretion following stimulation of the anterior region of the thalamus. These findings may be interpreted as indicative of existences in the diencephalon of excitatory and inhibitory central nervous system mechanisms for the control of the adrenal medullary secretion.

Adrenal Medulla↗

Effect of intestinal amino acid infusions on hypothalamic single unit activity in the anesthetized cat.

Single unit discharges in the ventromedial hypothalamic nucleus (VMH) and lateral hypothalamic area (LH) were recorded extracellularly in anesthetized cats, while amino acid solutions were perfused through the small intestine via implanted cannulae. Test infusions consisted of 5 amino acid mixtures (arginine, leucine, phenylalanine, tryptophan, alanine: 50 mM each), 5.0% casein hydrolysate; arginine 125 mM (2.2%); leucine 125 mM (1.6%). Sixty-six units were recorded in 30 cats. Of 52 tested in the LH, 19 or 37% were affected: 14 increased and 5 decreased in firing rate in response to amino acid intestinal perfusions with a very short latency consistent with activation of intestinal amino acid receptors. Of 14 neurons tested in VMH, only 3 or 21% were activated by amino acid infusions but with a long latency of several minutes which cannot exclude the involvement of a postabsorptive signal. Results are discussed in terms of intestinal afferent control over hypothalamic neuronal activity related to amino acid induced satiety.

Amino Acids↗

Descending projections of infralimbic cortex that mediate stimulation-evoked changes in arterial pressure.

The infralimbic cortex (IL) of the rat can modify autonomic nervous system activity, but the critical pathway(s) that mediate this influence are unclear. To define the potential pathways, the first series of experiments characterizes the descending projections of IL and the neighboring cortical areas using Phaseolus vulgaris leucoagglutinin (PHA-L). IL has prominent projections to the central nucleus of the amygdala (Ce), the mediodorsal nucleus of the thalamus (MD), the lateral hypothalamic area (LHA), the periaqueductal gray (PAG), the parabrachial nucleus (Pb), and the nucleus of the solitary tract (NTS). The density and selectivity of these projections suggest that the LHA and the PAG mediate the ability of the IL to regulate cardiovascular function. The second series of experiments demonstrates that locally anesthetizing neurons in either the LHA or PAG with lidocaine attenuates the hypotensive effects produced by electrical stimulation of the IL. Similarly, microinjections of cobalt chloride (a neurotransmission blocker) into the anterior portion of the LHA also decrease the arterial pressure responses to IL stimulation, suggesting that the ability of lidocaine to reversibly block the evoked response is due to inactivation of neurons in the LHA. These data indicate that hypotension evoked by stimulation of IL is mediated, at least in part, by direct or indirect projections to the LHA and through the PAG.

Animals↗

Role of hypothalamic monoamines in nicotine-induced anorexia in menopausal rats.

BACKGROUND: Nicotine reduces body weight by reducing appetite. Estradiol modulates food intake. Menopause or ovariectomy (Ovx) increases food intake and body weight. Nicotine and estradiol individually influence hypothalamic dopamine (DA) and serotonin (5-HT), whose interaction influences food intake and body weight. We investigated whether lower weight gain in menopausal smokers is mediated via changes in hypothalamic DA/5-HT. METHODS: Ovx or sham-operated female rats had 2 microdialysis guide cannulas simultaneously implanted in ipsilateral ventromedial nucleus of hypothalamus (VMN) and contralateral lateral hypothalamic area (LHA). Rats were divided into 4 groups and received a continuous subcutaneous infusion of nicotine or saline Ovx and sham. DA and 5-HT in LHA and VMN were measured by in vivo microdialysis. RESULTS: Nicotine infusion decreased food intake and body weight in Ovx and sham groups. Increase in LHA-DA and VMN-5-HT in sham group occurred with nicotine, whereas an increase in VMN-DA in Ovx groups with and without nicotine and VMN-5-HT in Ovx group with nicotine was observed. CONCLUSIONS: In the presence of estradiol (ovary intact sham-operated rats), nicotine lowers food intake and body weight via increased LHA-DA and VMN-5-HT. In menopause (Ovx rats), nicotine lowers food intake and body weight only via increased VMN-DA and 5-HT. Data show that lower weight gain is mediated via changes in hypothalamic monoamines, primarily via ventromedial hypothalamus.

Animals↗

Hypoglycemia activates orexin neurons and selectively increases hypothalamic orexin-B levels: responses inhibited by feeding and possibly mediated by the nucleus of the solitary tract.

Orexins are novel appetite-stimulating peptides expressed in the lateral hypothalamic area (LHA), and their expression is stimulated by hypoglycemia in fasted rats. We investigated activation of orexin and other neurons during insulin-induced hypoglycemia using the immediate early gene product Fos. Insulin (50 U/kg) lowered plasma glucose by >50% after 5 h and stimulated feeding sixfold compared with saline-injected controls. Hypoglycemic rats allowed to feed and normoglycemic controls both showed sparse Fos-positive (Fos+) neurons in the LHA and the paraventricular nucleus (PVN) and arcuate nucleus (ARC) and showed none in the nucleus of the solitary tract (NTS), which relays visceral feeding signals to the LHA. In the LHA, total numbers of Fos+ neurons were comparable in fed hypoglycemic and control groups (60 +/- 6 vs. 52 +/- 4 cells/mm2, P > 0.05), as were Fos+ neurons immunoreactive for orexin (1.4 +/- 0.4 vs. 0.6 +/- 0.4 cells/mm2, P > 0.05). By contrast, hypoglycemic rats that were fasted showed significantly more Fos+ nuclei in the LHA (96 +/- 10 cells/mm2, P < 0.05, vs. both other groups) and Fos+ orexin neurons (8.4 +/- 3.3 cells/mm2, P < 0.001, vs. both other groups). They also showed two- to threefold more Fos+ nuclei (P < 0.001) in the PVN and ARC than both fed hypoglycemic rats and controls and showed strikingly abundant Fos+ neurons in the NTS and dorsal motor nucleus of the vagus. In parallel studies, whole hypothalamic orexin-A levels were not changed in hypoglycemic rats, whether fasted or freely fed, whereas orexin-B levels were 10-fold higher in hypoglycemic fasted rats than in control and hypoglycemic fed groups. These data support our hypothesis that orexin neurons are stimulated by falling glucose levels but are readily inhibited by signals related to nutrient ingestion and suggest that they may functionally link with neuronal activity in the NTS. Orexin-A and -B may play specific roles in behavioral or neuroendocrine responses to hypoglycemia.

Animals↗

Topographical organization in the nucleus accumbens of afferents from the basolateral amygdala and efferents to the lateral hypothalamus.

The basolateral region of the amygdala and the lateral hypothalamic area are involved in cardiovascular regulation. The aim of the present investigation was to determine if the terminal field of afferent projections from the basolateral nucleus of the amygdala to the nucleus accumbens overlap with the origin of the efferent projections from the nucleus accumbens to the lateral hypothalamic area. Neurons projecting from the nucleus accumbens to the lateral hypothalamic area were labeled by injecting the retrograde tracer Fluoro-Gold in the lateral hypothalamus of rats. In the same rats, fiber terminals from the amygdala to the nucleus accumbens were labeled by injecting the anterograde tracer Fluoro-Ruby in the basolateral region of the amygdala. Injections of Fluoro-Gold in the lateral hypothalamus labeled neurons in the posteromedial portion of the nucleus accumbens. Injections of Fluoro-Ruby in the basolateral amygdala labeled fibers and terminals in all parts of the nucleus accumbens with the highest density being found in the posteromedial part of the nucleus accumbens where Fluoro-Gold-labeled neurons were located. When regions of the posteromedial nucleus accumbens were examined under high-magnification, Fluoro-Ruby-labeled terminals appeared to make contact on Fluoro-Gold-labeled dendrites and cell bodies. This investigation demonstrates that there is a distinct overlap in the posteromedial region of the nucleus accumbens between the terminal field from neurons originating in the amygdala and neurons which project to the lateral hypothalamus. In addition, neurons in the basolateral amygdala appear to make synaptic contact with neurons in the nucleus accumbens that project to the lateral hypothalamic area.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

Role of the septal area in feeding behavior elicited by electrical stimulation of the lateral hypothalamus of the rat.

1. The present study was undertaken to investigate the influence of the septal area on neural mechanisms involved in feeding behavior elicited by electrical stimulation of the lateral hypothalamic area of the rat. 2. Electrolytic damage to medial and lateral septal nuclei induced a significant increase (18.29 +/- 1.69 to 25.05 +/- 2.31 g, P less than 0.05, N = 14) in food intake elicited by hypothalamic stimulation. The threshold current for stimulus-induced eating decreased by 20% after septal lesion. 3. A significant decrease in food ingestion was observed after electrical stimulation of the septal nuclei, either preceding (27.47 +/- 1.57 to 19.30 +/- 2.06 g, P less than 0.05, N = 13) or simultaneous (26.20 +/- 1.60 to 12.10 +/- 2.40 g, P less than 0.05, N = 11) with hypothalamic stimulation. 4. The results indicate an inhibitory effect of the septum on the lateral hypothalamic area and also suggest that the functional state of the lateral hypothalamus, which is responsible for the feeding behavior, depends on the activity pattern of the septal area.

Animals↗

[The neurons of the right and left prefrontal areas of the rat cerebral cortex and the stimulation of emotiogenic zones].

The effect of emotions on unit activity of the prefrontal cortex (right and left hemispheres) was studied in rats under conditions of stimulation of emotionally positive (lateral hypothalamic area) and negative (dorsomedial tegmentum) structures. The stimulation produced changes in unit activity of both the right and left hemispheres. Asymmetry was revealed in neuronal responses of the right and left areas of the prefrontal cortex: during emotionally positive stimulation the unit activity in the left cortex was more intensive, and the neurons of the right cortex were more active during the negative stimulation. In case of the negative emotional stimulation the greater asymmetry in neuronal responses was observed at contralateral stimulation, at the positive stimulation both the left and right localizations were equally effective.

Animals↗

2,5-Anhydro-D-mannitol: its unique central action on food intake and blood glucose in rats.

Peripheral administration of D-fructose has been reported to decrease food intake, and its 2-deoxy analogue, 2,5-anhydro-D-mannitol (2,5-AM), increased food intake and decreased blood glucose in rats. In the present study, 2,5-AM was selected for comparison with well-known 2-deoxy analogues of glucose. Infusion of 2,5-AM into the rat third cerebroventricle at 11.00 h induced feeding dose dependently (Y = 0.63 logX-1.20, r = 0.95, P less than 0.05). Rats treated with 2,5-AM at a maximal effective dose of 24 mumol/rat ate meals most persistently (P less than 0.05). No periprandial drinking was observed. Ambulatory activity increased concomitantly with feeding, but did not exceed the activity normally associated with a meal. Infusion of 24 mumol 2,5-AM into the third cerebroventricle induced no substantial change in plasma glucose or insulin in any 60-min experimental period. Unilateral microinfusion of 1.2 mumol 2,5-AM induced feeding in all 6 rats (P less than 0.01) when a cannula tip was located in the ventromedial hypothalamic nucleus (VMH), but not in the lateral hypothalamic area (LHA). These findings indicate that feeding elicitation may be due to disinhibition by 2,5-AM through the VMH. This is quite unique compared to the action mechanisms of hexose, pentose and their analogues, except 2,5-AM.

Animals↗

Nicotine administration decreases nitric oxide synthase expression in the hypothalamus of food-deprived rats.

Effect of nicotine on nitric oxide synthase (NOS) expression in various hypothalamic regions was investigated in rats via nicotineamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry. Sprague-Dawley rats were divided into the fed group, the fed and nicotine-treated group, the food-deprived group, and the food-deprived and nicotine-treated group. The fed groups received abundant food and water, while food was withheld from the food-deprived groups for 48 h. The nicotine-treated groups were injected with nicotine. Following food deprivation, enhanced NAPDH-d expression was detected in the paraventricular nucleus, ventromedial hypothalamic nucleus, and lateral hypothalamic area of the hypothalamus. Nicotine administration to the food-deprived rats resulted in decreased NADPH-d positivity. The present results indicate that nicotine administration is effective in limiting the enhancement in NOS expression following food restriction.

Animals↗

Chemical and neuronal control of feeding motivation.

The sugar acids, 3,4-dihydroxybutanoic acid gamma-lactone, 2-buten-4-olide and 2,4,5-trihydroxy pentanoic acid gamma-lactone which were found in blood modulate feeding behavior of rats by modifying neuronal activity in the lateral hypothalamic area [LHA] and the ventromedial hypothalamic nucleus [VMH]. The former two act as satiety substances and the latter as a hunger substance. Detection of changes in the concentration of these sugar acids in the blood by glucoreceptor neurons in the VMH and glucose-sensitive neurons in the LHA is important in the regulation of feeding. A phasic increase in fibroblast growth factor [FGF] was found in the cerebrospinal fluid after feeding. Cerebroventricular application of acidic FGF suppresses food intake. Interleukin-1 beta and tumor necrosis factor which have a quite similar amino acid sequence as FGF also suppress feeding. The neuronal mechanism of satiety action of these polypeptides is the same as the sugar acids. The results indicate that these endogenous substances participate in the central regulation of feeding. Hierarchial organization of the endogenous chemical information processing system which is composed of the viscera, medulla, hypothalamus and the cortex is discussed.

Animals↗

Central action of glucagon in rat hypothalamus.

The effects of electrophoretically applied glucagon on neuronal activity in the rat lateral hypothalamic area (LHA), dorsomedial hypothalamic nucleus (DMH), and ventromedial hypothalamic nucleus (VMH) were examined. In the LHA glucagon significantly suppressed the activity of glucose-sensitive neurons compared with its effect on non-glucose-sensitive neurons. This inhibitory effect of glucagon on LHA neurons was blocked by ouabain. Intracellular recordings from LHA neurons revealed that glucagon hyperpolarized the cell membrane without a significant change in the input membrane resistance. Intra-arterial injection of glucagon suppressed the activity of some neurons that were suppressed by electrophoretically applied glucagon. Similarly, glucagon suppressed the activity of significant numbers of DMH and VMH neurons with doses higher than those that affected LHA glucose-sensitive neurons. Cortical neurons were unaffected by glucagon. The data suggest that blood-borne glucagon could suppress the activity of LHA glucose-sensitive neurons and, in addition, might contribute to the control of metabolism and the termination of feeding behavior.

Animals↗

Inhibition of spinal dorsal horn neuronal responses to noxious skin heating by lateral hypothalamic stimulation in the cat.

The responses of single lumbar dorsal horn units to noxious radiant heating (50 degrees C, 10 s) of glabrous foot pad skin were recorded in cats anesthetized with sodium pentobarbital and 70% N2O. The heat-evoked responses of each of 38 units were markedly reduced during electrical stimulation (100-ms trains at 100 Hz, 3/s, 25-300 microA) in the lateral hypothalamic area (LH). LH sites at which stimulation inhibited dorsal horn unit heat-evoked responses were mapped by systematically varying the position of the stimulating electrode. Inhibition was generated at posterior through anterior hypothalamic levels in a region extending laterally from the periventricular gray (PVG) to the cerebral peduncles on both sides and ventrally to the base of the brain. The magnitude of inhibition increased with graded increases in LH stimulation intensity. Respective mean current intensities at threshold for generating inhibition were 27.6 +/- 17.4 (SD) microA for contralateral and 30.1 +/- 23.7 microA for ipsilateral LH stimulation. Dorsal horn unit responses to a series of graded noxious heat stimuli generally increased linearly from threshold (38-45 degrees C) to 52 degrees C. The slopes of such linear temperature-response functions were reduced, with no significant change in threshold, when the temperature series was repeated during concomitant ipsilateral LH stimulation. Contralateral LH stimulation produced similar slope reductions but additionally produced a significant mean threshold increase of 1.7 degrees C. The inhibitory effect of LH stimulation was significantly reduced in nine units from a mean of 28 +/- 18% of control to a mean of 59 +/- 18% following systemic administration of the serotonin (5-hydroxytryptamine, 5-HT) antagonist, methysergide (0.3-1 mg/kg). Possible functional relationships of LH with brain stem inhibitory systems and its role in analgesic mechanisms are discussed.

Animals↗

Spatio-temporal dynamics of brain activated regions during drinking behavior in rats.

Spatio-temporal dynamics of activated brain areas induced by drinking were investigated and visualized in behaving rats using functional magnetic resonance imaging (fMRI). The rats were trained to drink in the magnet bore, and the images were taken during and after drinking glucose and distilled water. During glucose ingestion, the signal intensity was increased continuously and maximally in the lateral hypothalamic area (LHA) and the ventromedial hypothalamus (VMH). Somewhat less intense activation in the central nucleus of the amygdala (AMc), and transient activation in the piriform cortex and the mediodorsal nucleus of the thalamus were observed. The signal intensities of other regions measured were largely unchanged. During post-ingestive periods, the signals re-increased in the hypothalamic areas and AMc. When water was given, LHA and VMH were similarly activated, however, the signal intensity in the amygdala was not significantly increased. The results indicate that these brain regions are activated differentially during drinking behavior, and that LHA and VMH play a central role in the control of not only feeding but also drinking. The regional activities in LHA and VMH are not principally related to the gustatory sensation, and the reactivation after drinking may be related to satisfaction or post-ingestive nutritional information. Also, the responses of AMc are probably due to reward value difference. To the best of our knowledge, this is the first report of mapping of brain areas using fMRI in behaving rats. The improved method described in this study for collecting fMRI data in behaving animals will be useful for studying functional network during animal behavior.

Animals↗

Influence of early undernutrition in rats on their body fat and RNA content in VMH neurons.

The RNA content of the ventromedial hypothalamus (VMH) and lateral hypothalamic area (LHA) neurons, and the epididymal, retroperitoneal, and liver fat content of 150-day-old male rats submitted to neonatal undernutrition, were investigated. The neonatal undernutrition was carried out by two different ways. First, by reducing the litters to two pups per nest from birth to weaning. The pups from normal litters (eight pups/nest) served as controls. Secondly, by separating half of the pups (four pups) from normal litters for 8 h daily during the first 5 postnatal days. The remaining nonseparated pups served as their controls. The data show that both groups of early undernourished pups had a significantly increased RNA content in the VMH neurons (RNA content in the LHA neurons was unchanged) and a significantly decreased epididymal, retroperitoneal, and liver fat content in comparison with their controls. The results indicate that early undernutrition leads to a permanent increase in the functional activity of VMH and alteration in fat metabolism in rats.

Adipose Tissue↗

Effects of restricted feeding on the activity of hypothalamic Orexin (OX)-A containing neurons and OX2 receptor mRNA level in the paraventricular nucleus of rats.

We have examined the effects of 3 weeks of food restriction on both the activity of neurons containing hypothalamic orexin (OX)-A and the level of OX receptor type 2 (OX2R) mRNA in the paraventricular nucleus (PVN) of rats. Double immunohistochemistry was used to examine the expression of OX-A and Fos in the lateral hypothalamic area (LHA), and in situ hybridization histochemistry was used to measure levels of OX2R mRNA in the PVN. After the period of restricted feeding, 20-30% of OX-A-containing neurons exhibited Fos-like immunoreactivity (LI). The distribution of OX-A-LI/Fos-LI cells in the food-restricted rats was similar to that observed in glucose-deprived rats after intracerebroventricular (icv) administration of 2-deoxy-D-glucose (2-DG). In addition, 3 weeks of food restriction caused a significant decrease in the expression of the OX2R gene in the parvocellular division of the PVN. These results suggest that the activation of OX-A-containing neurons induced by restricted feeding may be involved in neuroendocrine responses to food restriction.

Animals↗