Biomedical subjects

S F Leibowitz

Publications and source records attributed to S F Leibowitz.

At least 37 records · Page 2Linked to original sources

PubMed1994

Hypothalamic neuropeptide Y, its gene expression and receptor activity: relation to circulating corticosterone in adrenalectomized rats.

Previous evidence has suggested a possible relationship between the adrenal steroid, corticosterone (CORT) and neuropeptide Y (NPY) in the brain. To provide a more systematic analysis of this interaction, the present study employed a variety of techniques, including in situ hybridization to measure NPY gene expression, radioimmunoassay to examine peptide levels and radioligand [125I]peptide YY (PYY) binding for analysis of peptide receptors. The results show that adrenalectomy (ADX), which caused a decline in CORT to levels < 0.3 micrograms %, has generally little impact on the hypothalamic NPY projection system under normal, basal conditions. This includes peptide gene expression or content in the area of its cell bodies (arcuate nucleus, ARC), in addition to peptide binding at its receptor sites. While it also includes peptide content at most hypothalamic terminal sites, there are three notable exceptions, namely, the medial paraventricular (PVN) and dorsomedial nuclei and medial preoptic area, where NPY nerve terminals and glucocorticoid receptors are particularly dense and the decline in CORT through ADX markedly reduces NPY content. In contrast, evidence obtained from CORT replacement in ADX rats shows that this steroid has profound impact on all components of the hypothalamic NPY system. This peptide-steroid interaction is apparent at the level of the cell body (ARC), as well as at the nerve terminal or receptor site (PVN and ARC), where CORT levels > 10 micrograms % strongly potentiate NPY gene expression, peptide content and radioligand binding. These and other findings suggest that this CORT-NPY interaction in the hypothalamus occurs physiologically under conditions, e.g., at the onset of the active feeding cycle, when circulating CORT normally rises.

Adrenalectomy↗

PubMed1994

Specificity of hypothalamic peptides in the control of behavioral and physiological processes.

This review summarizes two model systems for understanding how brain neurochemicals, in conjunction with peripheral endocrine and metabolic processes, may be active in controlling very different functions in relation to energy and nutrient balance. As proposed, these systems are unquestionably oversimplified; however, they generate testable hypotheses for future investigations that will help to advance and revise these working models, as well as those of other peptide systems in the brain. Under normal conditions, these peptide systems are behaviorally and endocrinologically specific, and they are activated at very different periods of the daily cycle and at different stages of development. However, under pathologic conditions, their specificity and rhythmicity may be greatly disturbed. This occurs in states involving hypercortisolemia along with hyperinsulinemia or insulin deficiency, when these peptide systems become chronically activated. To determine whether this increased activity actually contributes to conditions of hyperphagia and obesity, and, thus, whether a reversal of this neurochemical activity may help in the treatment of these conditions, critical studies with various pharmacological manipulations are required. Of equal importance are investigations examining the development of these pathologic conditions, from birth to maturity, and their associated disturbances in neurochemical and endocrine processes. A thorough understanding of gene expression in localized brain areas and the contribution of various transcription factors to this process should allow the identification and development of methods that are useful in the treatment, as well as prevention, of disturbed patterns of nutrient intake, fat deposition, and body weight gain.

Animals↗

PubMed1994

Galanin-containing neurons in the paraventricular nucleus: a neurochemical marker for fat ingestion and body weight gain.

The physiological function of the peptide galanin (Gal) remains to be established. It is known to exist in high concentrations within the hypothalamus and to modulate the secretion of specific hormones, as well as to potentiate food consumption. Our study provides evidence for an essential function of neuronal Gal, within a specific hypothalamic area, in stimulating the behavioral process of fat ingestion and body weight gain. Through analyses of peptide levels via RIA and of gene expression via in situ hybridization, a close positive association is established between Gal in the paraventricular nucleus (PVN), particularly its midlateral region, and fat ingestion. No such relationship is detected for Gal in other brain areas or between PVN Gal and ingestion of carbohydrate or protein, supporting the behavioral and anatomical specificity of this relationship. Through PVN injection studies with antisense oligonucleotides to Gal mRNA, a dramatic decline in fat ingestion and body weight suggests that endogenous Gal contributes to the natural appetite for fat. Thus, Gal in the PVN is identified as a neurochemical marker for fat ingestion and, consequently, body weight gain.

Analysis of Variance↗

PubMed1994

Intracerebroventricular injection of dibutyryl cyclic adenosine 3',5'-monophosphate increases hypothalamic levels of neuropeptide Y.

This investigation examined in vivo the relationship between the nucleotide cAMP and hypothalamic levels of two peptides, neuropeptide Y (NPY) and galanin (GAL), which are known to potentiate feeding behavior. In brain-cannulated rats, third ventricular injections of N6,2'-O-dibutyryl cyclic adenosine 3',5'-monophosphate ((Bu)2cAMP, 25 micrograms), compared to saline, caused a significant increase in NPY levels in the arcuate nucleus (ARC) and medial parvocellular portion of the paraventricular nucleus (mPVN), while having no impact in other hypothalamic areas. These site-specific changes in NPY occurred in the absence of any alteration in circulating levels of insulin, corticosterone, aldosterone or glucose, or of changes in hypothalamic levels of GAL. These findings implicate cAMP as having regulatory functions within specific hypothalamic NPY-synthesizing neurons, projecting from the ARC to the mPVN, that are believed to be involved in energy homeostasis.

Aldosterone↗

PubMed1994

Hypothalamic neuropeptide Y and its gene expression: relation to light/dark cycle and circulating corticosterone.

The hypothalamic neuropeptide Y (NPY) system, along with levels of circulating corticosterone (CORT), were examined in rats at different times across the light/dark cycle. Tissue samples were taken from the mediobasal hypothalamus (MBH), which contains the primary hypothalamic NPY cell group of the arcuate nucleus (ARC), and the mediodorsal (MDH) hypothalamus, which contains the paraventricular and dorsomedial nuclei that receive a dense NPY innervation from the ARC. In these dissections, measurements of NPY mRNA and peptide levels were taken using a solution hybridization/nuclease protection assay procedure and radioimmunoassay. The results demonstrate that (i) NPY mRNA levels in the MBH, but not MDH, vary significantly in relation to the light/dark cycle, showing a sharp rise 4-6 h before dark onset, sustained high levels over the next 3-4 h and then, a sharp decline 1 h before dark onset; (ii) this rise in NPY mRNA in the MBH before dark onset, while associated with stable levels of MBH NPY during this time, is followed 2-4 h later, around dark onset, by a rise in NPY peptide levels of the MDH simultaneous to a decrease in NPY levels of the MBH; (iii) levels of circulating CORT shift dramatically across the light-dark cycle, exhibiting an increase from basal levels (< 0.3 microgram/dl) to 5 micrograms/dl approximately 4 h before dark onset, a further rise that peaks at 26 micrograms/dl around dark onset, and then a significant decline to 16 micrograms/dl at 2 h after dark onset; and (iv) there exists a positive relationship between CORT and NPY mRNA or peptide levels in the MBH during the 4-6 h before dark onset, while in the MDH, a positive relationship between this steroid and NPY peptide levels is obtained at dark onset. It is proposed that these rhythms, involving a predark rise in CORT and NPY gene expression leading to a peak in CORT and peptide levels at dark onset, are active in stimulating feeding behavior, particularly carbohydrate ingestion, which predominates at that time.

Adrenocorticotropic Hormone↗

PubMed1994

Hypothalamic galanin-like immunoreactivity and its gene expression in relation to circulating corticosterone.

The neuropeptide galanin (GAL), which exists in dense concentrations within the hypothalamus, has physiological actions which are neuroendocrine in nature. In light of evidence showing GAL to alter the release of the adrenal steroid, corticosterone (CORT), a possible effect of this steroid on GAL gene expression and peptide production in discrete hypothalamic and brainstem sites was investigated. Using radioimmunoassay and in situ hybridization techniques, this peptide was examined in rats that had received SHAM surgery, adrenalectomy (ADX) and ADX+CORT replacement. The results showed a clear, site-specific change in GAL in relation to circulating CORT. A loss of CORT after ADX caused a dramatic decline in GAL peptide and mRNA levels in the arcuate nucleus and peptide levels in the median eminence, with no change occurring in other hypothalamic areas. In the brainstem, a similar change was detected in the dorsal raphe nucleus but not the locus coeruleus. The GAL peptide and mRNA levels in these specific brain areas of ADX rats was restored by CORT replacement, which had no impact on GAL in other brain sites. These findings demonstrate that CORT's impact on brain GAL is highly site specific, possibly determined by local concentrations of steroid receptors.

Adrenal Glands↗

PubMed1994

Specific inhibition of endogenous neuropeptide Y synthesis in arcuate nucleus by antisense oligonucleotides suppresses feeding behavior and insulin secretion.

Neuropeptide Y (NPY), which is synthesized in neurons of the arcuate nucleus (ARC) that project to different hypothalamic nuclei, is known to have potent effects on eating behavior and hormone secretion after hypothalamic administration. To test the hypothesis that endogenous NPY is essential for the normal expression of these responses, the present study used to unmodified antisense oligodeoxynucleotides (ODNs) to disrupt the synthesis of NPY in the ARC and to examine the impact of this disturbance on nutrient intake, as well as on circulating levels of insulin and the adrenal steroids, corticosterone and aldosterone. Brain-cannulated rats maintained on macronutrient diets were given daily, bilateral injections, over a 4-day period, of NPY antisense ODNs, sense ODNs or saline into the ARC. The NPY antisense ODNs produced a significant decline (-33% relative to sense ODNs and -40% relative to saline, P < 0.05) in NPY levels in this nucleus, without causing any direct neural damage. Peptide levels in other hypothalamic areas, namely, the paraventricular nucleus and medial preoptic nucleus, were not significantly affected. In association with this reduction in ARC NPY, the antisense-treated animals exhibited a significant decrease in feeding behavior measured during the first 90 min of the natural feeding cycle, as well as over the 24-h period. In the 90-min interval, both carbohydrate and fat intake were suppressed by 65-70% (P < 0.05, relative to both saline and sense ODNs control scores).(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

PubMed1994

Diurnal rhythm of galanin-like immunoreactivity in the paraventricular and suprachiasmatic nuclei and other hypothalamic areas.

The peptide galanin (GAL), when injected into the rat hypothalamus, is known to stimulate feeding behavior and affect the secretion of various hormones, including insulin and the adrenal steroid, corticosterone. To determine whether endogenous peptide levels shift in relation to natural rhythms of feeding and circulating hormone levels, rats were sacrificed at different times of the light/dark cycle, and their GAL levels were measured, via radioimmunoassay, in medial hypothalamic dissections and micropunched hypothalamic areas. The results suggest the existence of two distinct diurnal rhythms for hypothalamic GAL. One rhythm, detected exclusively in the area of the SCN, is characterized by bimodal peaks of GAL, threefold higher than basal peptide levels, around the onset of the dark and light periods. The second rhythm shows a single peak of GAL towards the middle of the nocturnal feeding cycle, specifically between the third and sixth hour. This latter rhythm is evident in the dorsal region of the medial hypothalamus, localized specifically to the lateral portion of the PVN. Moreover, it is inversely related to circulating insulin but unrelated to the adrenal steroids, suggesting a possible association between this pancreatic hormone and GAL in the PVN.

Aldosterone↗

PubMed1994

Adrenal steroid receptors: interactions with brain neuropeptide systems in relation to nutrient intake and metabolism.

The glucocorticoid, corticosterone (CORT), is believed to have an important function in modulating nutrient ingestion and metabolism. Recent evidence described in this review suggests that the effects of this adrenal hormone are mediated through two steroid receptor subtypes, the type I mineralocorticoid receptor and the type II glucocorticoid receptor. These receptors, which have different affinities for CORT, respond to different levels of circulating hormone. They mediate distinct effects of the steroid, which can be distinguished by the specific nutrient ingested and by the particular period of the circadian cycle. Under normal physiological conditions, the type I receptor is tonically activated, either by low basal levels of circulating CORT (0.5-2 microgram %) normally available across the circadian cycle or possibly by the mineralocorticoid aldosterone. This type I activation is required for the maintenance of fat ingestion and fat deposition that occurs during most meals of the feeding cycle. In contrast, the type II receptor is phasically activated by moderate levels of CORT (2-10 micrograms %) normally reached during the circadian peak. Activation of this receptor is required for the natural surge in carbohydrate ingestion and metabolism that is essential at the onset of the active feeding cycle when the body's glycogen stores are at their nadir, and gluconeogenesis is needed to maintain blood glucose levels. This receptor is also activated during periods of increased energy requirements, such as, after exercise and food restriction, when CORT levels rise further (> 10 micrograms %) and when its catabolic effects on fat and protein stores predominate to provide additional substrates for glucose homeostasis. These functions of CORT on fat and carbohydrate balance are mediated, in part, by type I and type II receptors located within the hypothalamic paraventricular nucleus, which is known to have key functions in controlling nutrient intake and metabolism, as well as circulating CORT levels. Moreover, the type II receptors within this nucleus, in addition to the arcuate nucleus, may interact positively with the peptide, neuropeptide Y, and the catecholamine, norepinephrine, both of which act to enhance natural carbohydrate feeding and CORT release at the onset of the natural feeding cycle. Thus, under normal conditions, endogenous CORT has a primary function in controlling nutrient ingestion and metabolism over the natural circadian cycle, through the coordinated action of the type I and type II steroid receptor systems. Through this action, CORT has impact on total caloric intake and body weight gain over the long term.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex Hormones↗

PubMed1994

Meal patterns of macronutrient intake in rats with particular dietary preferences.

In the present study, we examined, via computer-assisted analyses, the nocturnal meal patterns of male albino Sprague-Dawley rats with clear differences in their individual preferences for the macronutrients, protein, carbohydrate, and fat. Rats exhibiting a strong preference for the carbohydrate diet over the 12-h nocturnal cycle (approximately 50% of the group) consumed fewer total calories and relatively small, more frequent meals, compared with rats that preferred protein or fat. Moreover, the first meal of the feeding cycle was identified as being most distinctive in reflecting the individual dietary preferences of these rats. This contrasts with the subsequent meals, which for all rats showed a general trend of increasing proportions of protein and fat and a decreasing concentration of carbohydrate. Only the high-fat rats (approximately 30% of the group) were further distinguished by a particularly large fat-predominant meal in the middle-dark period, which was then followed by smaller fat-rich meals in the late-dark period. These fat-preferring rats exhibited significantly greater body weight gain compared with rats preferring carbohydrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Nutritional Physiological Phenomena↗

PubMed1993

Neuropeptide Y projection from arcuate nucleus to parvocellular division of paraventricular nucleus: specific relation to the ingestion of carbohydrate.

Neuropeptide Y (NPY) injection into the hypothalamic paraventricular nucleus (PVN) stimulates feeding behavior and specifically carbohydrate intake in rats. The present study investigated the relation between endogenous levels of NPY and natural ingestion for carbohydrate. It also examined the possible importance of a specific NPY projection in this relationship, which traverses from cell bodies in the arcuate nucleus (ARC) to terminals in the parvocellular division of the PVN (pPVN). Sprague-Dawley rats were given pure macronutrient diets (carbohydrate, protein and fat), and their daily nutrient intake was recorded for 3 weeks. The rats were sacrificed, and 8 hypothalamic nuclei were micropunched and examined via RIA for endogenous NPY levels. The results demonstrate a strong, positive correlation between daily carbohydrate intake and hypothalamic NPY levels. The relationship was specific to the pPVN (r = +0.71; P < 0.001), ARC (r = +0.57; P < 0.001) and dorsomedial nucleus (DMN, r = +0.52; P < 0.01), and was not observed in any other hypothalamic area, including the magnocellular division of the PVN. In the pPVN, the NPY levels of animals that consumed > 50 kcal of carbohydrate (49 pg/microgram protein) were almost twice that of animals that consumed < 20 kcal of carbohydrate (28 pg/microgram protein: P < 0.01). Furthermore, NPY levels in the ARC were positively correlated with NPY in the pPVN and DMN but not any other nuclei. No relation between hypothalamic NPY and measures of protein or fat ingestion was detected. Levels of NPY were also unrelated to total caloric intake, to body weight at sacrifice, and to body weight gain during the 3-week measurement period. These results, together with other findings, provide support for a role of endogenous NPY and its projection from the ARC to the pPVN, perhaps via the DMN, in controlling natural appetite for carbohydrate.

Animals↗

PubMed1993

Neuropeptide Y in the arcuate nucleus is modulated by alterations in glucose utilization.

This study examined the response of hypothalamic neuropeptide Y (NPY) to specific metabolic challenges. After intraperitoneal administration of 2-deoxy-D-glucose, which blocks glucose utilization, NPY levels measured via radioimmunoassay were significantly potentiated in the arcuate (ARC) and suprachiasmatic nuclei of the rat hypothalamus. The antimetabolite mercaptoacetate, in contrast, which blocks fatty acid oxidation, produced no significant change and actually tended to reduce NPY levels in the ARC. It is concluded that glucose utilization, in particular, may constitute an important signal, either direct or indirect, in the modulation of NPY production in the hypothalamus.

Animals↗

PubMed1993

Central opioid receptor subtype antagonists differentially reduce intake of saccharin and maltose dextrin solutions in rats.

Opioid modulation of ingestion includes general opioid antagonism of deprivation-induced water intake and intake of sucrose and saccharin solutions. Previous studies using selective subtype antagonists indicated that opioid effects upon deprivation-induced water intake occurred through the mu2 receptor and that opioid effects upon sucrose intake occurred through kappa and mu2 receptors. The present study compared the effects of intracerebroventricular administration of opioid receptor subtype antagonists upon intakes of a saccharin solution and a maltose dextrin (MD) solution to determine which receptor subtypes were involved in modulation of ingestion of different preferred tastants. Significant reductions in saccharin intake (1 h) occurred following naltrexone (20-50 micrograms: 66%) and naltrindole (delta, 20 micrograms: 75%), whereas [D-Ala2, Leu5, Cys6]-enkephalin (DALCE, delta 1, 40 micrograms: 45%) had transient (5 min) effects. Neither beta-funaltrexamine (B-FNA, mu), naloxonazine (mu1), nor nor-binaltorphamine (Nor-BNI, kappa) significantly altered saccharin intake. Significant reductions in MD intake (1 h) occurred following naltrexone (5-50 micrograms: 69%) and B-FNA (1-20 micrograms: 38%). MD intake was not reduced by naltrindole, DALCE, naloxonazine and Nor-BNI. Peak antagonist effects were delayed (20-25 min) to reflect interference with the maintenance, rather than the initiation of saccharin or MD intake. Comparisons of opioid antagonist effects across intake situations revealed that naltrexone had consistently low ID40 values for saccharin (29 nmol), MD (25 nmol), sucrose (6 nmol) and deprivation (38 nmol) intake. Despite its significant effects relative to naloxonazine, B-FNA had significantly higher ID40 values for saccharin (800 nmol), MD (763 nmol) and sucrose (508 nmol) relative to deprivation (99 nmol) intake, suggesting that mu2 receptors may be mediating maintenance of intake rather than taste effects. Nor-BNI had low ID40 values for intake of sucrose (4 nmol), but not for saccharin (168 nmol), MD (153 nmol) and deprivation (176 nmol), suggesting that kappa receptors may mediate ingestion of sweet-tasting stimuli. That delta (naltrindole: ID40 = 60 nmol), but not delta 1 (DALCE: ID40 = 288 nmol) antagonists consistently reduce saccharin intake suggests a role for the delta 2 receptor subtype in the modulation of hedonic orosensory signals.

Animals↗

PubMed1993

The paraventricular nucleus is uniquely responsive to the feeding stimulatory effects of steroid hormones.

The paraventricular nucleus is uniquely responsive to the feeding stimulatory effects of steroid hormones (Tempel, D.L., Kim, T. and Leibowitz, S.F. Brain Research 00: 000-000). This study tested the effects of hypothalamic as well as extrahypothalamic implants of the adrenal steroids, corticosterone (CORT) and aldosterone (ALDO), on food intake and macronutrient selection in sham-operated and adrenalectomized (ADX) rats 1 h after administration. Consistent with a previous experiment, implants of CORT and ALDO in the hypothalamic paraventricular nucleus (PVN) were effective in stimulating food intake. These tests, conducted at the onset of the active feeding cycle, showed PVN implants of CORT to potentiate specifically carbohydrate intake in ADX rats, while having no effect in sham rats. This was in contrast to PVN ALDO which predominantly stimulated fat intake in sham as well as ADX rats. Neither CORT nor ALDO had any effect on food intake after implantation into other hypothalamic or extrahypothalamic sites tested. These unresponsive hypothalamic sites were the dorsomedial and ventromedial nuclei, perifornical lateral hypothalamus, and arcuate nucleus. Extrahypothalamic sites including the dorsal CA1 region of the hippocampus, the central nucleus of the amygdala and the lateral septum were also unresponsive to steroid implants. These results identify the PVN, and the steroid receptors located within it, as having a specific function in mediating the action of CORT and ALDO on carbohydrate and fat intake, respectively.

Adrenalectomy↗

PubMed1993

Microdialysis analysis of norepinephrine levels in the paraventricular nucleus in association with food intake at dark onset.

It has been proposed that norepinephrine (NE) in the paraventricular nucleus (PVN) acts to stimulate carbohydrate feeding specifically at the start of the active (dark) cycle in rats. This study used microdialysis to examine the relationship between endogenous levels of NE in the PVN at dark onset and the amount of food consumed at this time. The results indicated that: (1) in satiated rats on a lab chow diet, NE levels in the PVN, as opposed to sites anterior or lateral to this nucleus, were significantly higher during large meals around dark onset then they were during small meals or during intervals that preceded the large meals, and (2) in food-deprived animals given a pure carbohydrate diet at dark onset, PVN levels of NE just before the initiation of the meal were significantly higher in animals that consumed a relatively large carbohydrate meal (> 2.0 g) during the first dark hour, and they were significantly correlated across animals with the size of their carbohydrate meal. These findings are consistent with other evidence linking endogenous PVN NE to food intake at the beginning of the natural feeding cycle.

Animals↗

PubMed1993

The perifornical area: the major focus of (a) patchily distributed hypothalamic neuropeptide Y-sensitive feeding system(s).

Neuropeptide Y (NPY), a neurochemical found in high concentrations within hypothalamic neurons, is believed to participate in the control of eating behavior and body energy balance and elicits a powerful eating response when injected into the hypothalamus. To delineate precisely the locus of this effect, NPY (78 pmol) or its artificial cerebrospinal fluid vehicle was injected in the extremely small volume of 10 nl through chronic guide cannulae into an array of 47 different hypothalamic areas in satiated rats and the elicited food intake was measured. To determine the anatomical resolution of this technique, the spread and recovery of [125I]NPY injected in 10 nl was also assessed. Results indicate that as much as 95% of the injected label was recovered within the brain tissue and guide cannulae and that 100% of the tissue label was localized to within 0.8 mm of the injection site. Behavioral results show that the perifornical hypothalamus (PFH), at the level of the caudal paraventricular nucleus, is the most sensitive hypothalamic site for NPY-induced eating. NPY there elicited mean increases in food intake of 12.5 g over baseline at 1 h and 20.0 g at 4 h postinjection. Injections bracketing the PFH in all directions were substantially less effective. Additionally, significant effects were also observed in at least seven other sites that were distributed throughout the hypothalamus. These findings suggest both that the PFH may be the primary hypothalamic site containing feeding-related NPY-sensitive receptors and that other sites distributed within the hypothalamus also can mediate NPY's effects.

Analysis of Variance↗

PubMed1993

Meal pattern analysis of macronutrient intake after PVN norepinephrine and peripheral clonidine administration.

Norepinephrine (NE) injected into the paraventricular nucleus (PVN) of the hypothalamus of rats is a potent stimulant of food intake, more specifically ingestion of the carbohydrate nutrient. In 2 experiments of the present study, this effect was found to be dose-dependent, and the effectiveness of NE in potentiating total food consumption was greatly reduced when the carbohydrate diet was removed. In addition, experiments using a computer-automated data acquisition apparatus were performed to characterize, in detail, the impact of PVN injection of NE and peripheral administration of the alpha2-noradrenergic agonist clonidine (CLON) on the macrostructure of feeding behavior in animals given 3 pure macronutrient diets. These 2 compounds, injected at the onset of the nocturnal feeding cycle, had very similar effects on meal patterns, with both affecting nutrient intake by increasing meal size and duration rather than by increasing meal frequency. They both affected primarily the first meal of the dark cycle, selectively enhancing carbohydrate ingestion by increasing Kcal intake, percent composition in the total diet and feeding time, and also by decreasing the satiating impact of this macronutrient. These stimulatory effects of NE and CLON on carbohydrate ingestion during the first meal were followed by complete recovery over the next 1 to 2 hours after injection. In addition to these predominant effects on carbohydrate intake, PVN NE at the highest doses tested (10 and 20 nmoles) produced a small increase in fat intake, whereas peripheral CLON actually decreased intake of fat and protein over the 12-hour cycle. The similarities in the impact of NE and CLON on carbohydrate feeding patterns support the hypothesis that both agonists may be acting via the same PVN alpha2-noradrenergic system controlling ingestion of the carbohydrate-rich meals which predominate at dark onset.

Adrenergic alpha-Agonists↗

PubMed1993

Meal patterns and macronutrient intake after peripheral and PVN injections of the alpha 2-receptor antagonist idazoxan.

Studies with idazoxan (IDA), a specific alpha 2-noradrenergic receptor antagonist, demonstrate effects on feeding behavior opposite to those observed with norepinephrine in the paraventricular nucleus (PVN) and peripheral injection of the alpha 2 agonist clonidine. Administration of IDA, both intraperitoneally (IP) and into the PVN at the onset of the nocturnal feeding cycle, caused a dose-related, selective suppression of carbohydrate intake 90 min after injection. To characterize further the impact of this antagonist on macronutrient intake, we examined in IDA-injected animals the macrostructure of feeding using computer-assisted analyses of meal patterns. Both IP and PVN administration of IDA produced a selective suppression of carbohydrate intake, primarily during the first meal of the feeding cycle. This effect occurred through significant reductions in meal size, diet composition, feeding time, and feeding rate for this nutrient. Idazoxan administration into the PVN continued to decrease carbohydrate intake in the next two meals and reduced the satiating impact of this nutrient. In contrast to this immediate change in carbohydrate intake, PVN IDA reduced protein intake after a latency of 4 h. although fat intake was suppressed only after a latency of 7 h. An increase in total meal number and a decrease in the average meal size across the 12-h dark cycle were seen after PVN IDA administration. These results, showing effects of peripheral and PVN-injected IDA on carbohydrate intake, suggest a possible physiological role of endogenous PVN alpha 2-noradrenergic receptors in modulating natural patterns of carbohydrate feeding at the onset of the dark period.

Adrenergic alpha-Antagonists↗