RESUMEN
OBJECTIVE: This study evaluated the effect of a protein, the isolated Trypsin Inhibitor (TTI) from Tamarindus indica L. seed, as a CCK secretagogue and its action upon food intake and leptin in obese Wistar rats. METHODS: Three groups of obese rats were fed 10 days one of the following diets: Standard diet (Labina®) + water; High Glycemic Index and Load (HGLI) diet + water or HGLI diet + TTI. Lean animals were fed the standard diet for the 10 days. Food intake, zoometric measurements, plasma CCK, plasma leptin, relative mRNA expression of intestinal CCK-related genes, and expression of the ob gene in subcutaneous adipose tissue were assessed. RESULTS: TTI decreased food intake but did not increase plasma CCK in obese animals. On the other hand, TTI treatment decreased CCK-1R gene expression in obese animals compared with the obese group with no treatment (p = 0.027). Obese animals treated with TTI presented lower plasma leptin than the non-treated obese animals. CONCLUSION: We suggest that TTI by decreasing plasma leptin may improve CCK action, regardless of its increase in plasma from obese rats, since food intake was lowest.
Asunto(s)
Depresores del Apetito/farmacología , Ingestión de Alimentos/efectos de los fármacos , Leptina/sangre , Obesidad , Proteínas de Vegetales Comestibles/farmacología , Receptores de Colecistoquinina/genética , Tamarindus/química , Animales , Depresores del Apetito/aislamiento & purificación , Depresores del Apetito/uso terapéutico , Regulación hacia Abajo/efectos de los fármacos , Expresión Génica/efectos de los fármacos , Masculino , Obesidad/sangre , Obesidad/tratamiento farmacológico , Obesidad/genética , Proteínas de Vegetales Comestibles/aislamiento & purificación , Ratas , Ratas Wistar , Receptores de Colecistoquinina/metabolismo , Respuesta de Saciedad/efectos de los fármacos , Semillas/químicaRESUMEN
Fibre is generally considered to dilute food energy, alter intestinal transit time and promote satiety; however, in cats, conflicting results have been found. In this study, two insoluble fibres were evaluated in four feline diets: control (no added fibre); diet with 10% sugar cane fibre; diet with 20% sugar cane fibre; and diet with 10% cellulose. The experiment was conducted with 32 cats, eight animals per diet, over 42 days: 1-7 for diet adaptation; 8-14 for total collection of faeces for digestibility; 15-17 for fresh faeces collection for fermentation products measurements; 18-20 for gastrointestinal transit time determination; 21 and 37 to evaluate the pattern of food intake; and 22 and 42 to assess satiety. Means were compared by analysis of variance and orthogonal contrasts, and the pattern of food intake was compared by repeated-measures analysis of variance (p < 0.05). The cats exhibited increased food intake after fibre addition to the diets (p < 0.05), achieving similar energy consumption. Cellulose and the two levels of sugar cane fibre reduced nutrient availability and energy digestibility, but only sugar cane fibre reduced fat digestibility (p < 0.05). Faecal output and the number of defecations per day increased with fibre inclusion (p < 0.05). Gastrointestinal transit time did not change with sugar cane fibre inclusion, but it was reduced with cellulose addition (p = 0.032). The pattern of food intake did not change, but cats fed fibre-supplemented diets exhibited greater consumption of a challenge meal, increasing energy intake (p < 0.01) when exposed to a palatable, energy-dense food.
Asunto(s)
Alimentación Animal/análisis , Gatos/fisiología , Dieta/veterinaria , Fibras de la Dieta/normas , Respuesta de Saciedad/efectos de los fármacos , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Femenino , MasculinoRESUMEN
RATIONALE: The searching for safe and effective antiobesity drugs has been the subject of intense research. Previous studies have shown several pharmacological applications of organoselenium compounds; however, their possible anorectic-like actions have not been investigated. OBJECTIVE: This study aims to investigate the effects of (PhSe)2 and (p-ClPhSe)2 on feeding behavior of rats and their potential as weight-reducing agents. METHODS: The effects of intraperitoneal administration of diselenides were investigated through the microstructural pattern of feeding behavior, behavioral satiety sequence (BSS), hypothalamic serotonin (5-HT) uptake, body weight, and epididymal fat content of male rats. RESULTS: Our findings demonstrated that food intake of fasted rats was reduced by both diselenides (1 and 10 mg/kg). Diphenyl diselenide [(PhSe)2] (1 mg/kg) and p-chloro-diphenyl diselenide [(p-ClPhSe)2] (10 mg/kg) decreased the frequency, mean duration, and mean size of meals compared with the control treatment. The BSS structure was preserved when organoselenium compounds (1 mg/kg) were administered, and it was associated to a displacement to the left when the resting period started indicating a satiating action. Inhibition of 5-HT uptake in the hypothalamus (â¼20 %) was also found in rats treated with low doses of (PhSe)2 and (p-ClPhSe)2 (1 mg/kg). Treatments with a high dose of both diselenides (10 mg/kg) carried out for 7 days induced weight loss and epididymal fat reduction in sated rats. CONCLUSION: This study suggests that diselenides caused a satiating action in rats that could be partially explained by the inhibition of hypothalamic 5-HT uptake. These organoselenium compounds were potential weight-reducing agents when repeatedly administered.
Asunto(s)
Derivados del Benceno/farmacología , Conducta Alimentaria/efectos de los fármacos , Compuestos de Organoselenio/farmacología , Respuesta de Saciedad/efectos de los fármacos , Animales , Peso Corporal/efectos de los fármacos , Peso Corporal/fisiología , Relación Dosis-Respuesta a Droga , Conducta Alimentaria/fisiología , Masculino , Ratas , Ratas Wistar , Respuesta de Saciedad/fisiologíaRESUMEN
Anorexia is a common clinical manifestation of primary adrenal gland failure. Adrenalectomy (ADX)-induced hypophagia is reversed by oxytocin (OT) receptor antagonist and is associated with increased activation of satiety-related responses in the nucleus of the solitary tract (NTS). This study evaluated OT projections from the paraventricular nucleus of the hypothalamus (PVN) to the NTS after ADX and the effect of pretreatment with intracerebroventricular injection of an OT receptor antagonist ([d(CH2)5,Tyr(Me)(2),Orn(8)]-vasotocin; OVT) on the activation of NTS neurons induced by feeding in adrenalectomized rats. Adrenalectomized animals showed higher OT labelling in the NTS than the sham and the ADX with corticosterone replacement (ADX + B) groups. Adrenalectomized animals exhibited co-localization of the anterograde tracer Phaseolus vulgaris leucoagglutinin and OT in axons in the NTS as well as OT fibres apposing NTS neurons activated by refeeding. After vehicle pretreatment, compared with fasting, refeeding increased the numbers of Fos- and Fos + TH-immunoreactive neurons in the NTS in sham, ADX and ADX + B groups, with a higher number of these immunolabelled neurons in adrenalectomized animals. Compared with fasting conditions, refeeding also increased the activation of NTS neurons in OVT-pretreated sham, ADX and ADX + B groups, but there was no difference among the three experimental groups. These data demonstrate that OT is upregulated in projections to the NTS following ADX and that OT receptor antagonist reverses the greater activation of NTS neurons induced by feeding after ADX. The data indicate that OT pathways to the NTS contribute to higher satiety-related responses and, thus, to reduce meal size in primary adrenal insufficiency.
Asunto(s)
Enfermedad de Addison/fisiopatología , Oxitocina/fisiología , Respuesta de Saciedad/efectos de los fármacos , Núcleo Solitario/fisiología , Adrenalectomía , Animales , Ingestión de Alimentos/fisiología , Fitohemaglutininas/farmacología , Ratas Sprague-Dawley , Receptores de Oxitocina/antagonistas & inhibidoresRESUMEN
Increased prevalence of obesity is associated with the growth of chronic degenerative diseases. One of the main factors associated with this increase is the change in nutritional status of individuals. Medium chain triglycerides (MCT) are rapidly metabolized and less stored in the adipose tissue, being a possible tool for weight control. In order to analyze the influence of consumption of this lipid on satiety, body composition and energy expenditure (EE), a literature review was performed of controlled clinical studies reported in PUBMED and ELSEVIER between the years 2000 and 2010. Fourteen articles were selected presenting short and long-term intervention. Among these, six showed a decrease in body mass of individuals, with consequent loss of weight. Only one showed a positive effect on satiation and four showed an increase in EE. Thus the results are inconclusive and there is a need for further controlled studies with standardized amounts of MCT, so that its use can become an alternative for obesity nutritional treatment.
Asunto(s)
Composición Corporal/efectos de los fármacos , Dieta , Metabolismo Energético/efectos de los fármacos , Respuesta de Saciedad/efectos de los fármacos , Triglicéridos/farmacología , Peso Corporal , Ingestión de Alimentos , Humanos , Obesidad/fisiopatologíaRESUMEN
Male rats allowed copulating without restriction with a single oestrous female ejaculate repeatedly until reaching sexual exhaustion. Twenty-four hours after this process, sexually exhausted males exhibit a series of physiological alterations when compared to non-exhausted males. Among them, the most conspicuous are a long-lasting sexual behaviour inhibition and a generalised hypersensitivity to drug actions. The objective of the present work was to establish if there was a correlation between these two features of sexual satiation in relation to the duration of its expression. To that aim, we characterised the spontaneous sexual behaviour recovery process from sexual satiation, as well as the duration of the drug hypersensitivity phenomenon. The latter was assessed through the appearance of a sign of the serotonergic syndrome: the flat body posture. Results showed that the drug hypersensitivity phenomenon and the sexual inhibition that results from copulation to satiation follow a similar time course of recovery, with a drastic decrease in their expression 96 h after the sexual satiation process. This finding indicates that these phenomena might represent two expressions of a same brain plasticity process, as suggested by the long lasting character of both events, which interestingly appears to be reversible.
Asunto(s)
Copulación/fisiología , Hipersensibilidad a las Drogas/fisiopatología , Conducta Sexual Animal/fisiología , Disfunciones Sexuales Fisiológicas/etiología , 8-Hidroxi-2-(di-n-propilamino)tetralin/efectos adversos , Análisis de Varianza , Animales , Relación Dosis-Respuesta a Droga , Eyaculación/fisiología , Femenino , Masculino , Postura/fisiología , Ratas , Ratas Wistar , Recuperación de la Función/efectos de los fármacos , Recuperación de la Función/fisiología , Respuesta de Saciedad/efectos de los fármacos , Respuesta de Saciedad/fisiología , Agonistas de Receptores de Serotonina/efectos adversos , Estadística como Asunto , Estadísticas no Paramétricas , Factores de TiempoRESUMEN
Adrenalectomy-induced hypophagia is associated with increased satiety-related responses, which involve neuronal activation of the nucleus of the solitary tract (NTS). Besides its effects on the pituitary-adrenal axis, corticotrophin-releasing factor (CRF) has been shown to play an important role in feeding behaviour, as it possesses anorexigenic effects. We evaluated feeding-induced CRF mRNA expression in the paraventricular nucleus (PVN) and the effects of pretreatment with CRF(2) receptor antagonist (Antisauvagine-30, AS30) on food intake and activation of NTS neurons in response to feeding in adrenalectomised (ADX) rats. Compared to the sham group, ADX increased CRF mRNA levels in the PVN of fasted animals, which was further augmented by refeeding. AS30 treatment did not affect food intake in the sham and ADX+corticosterone (B) groups; however, it reversed hypophagia in the ADX group. In vehicle-pretreated animals, refeeding increased the number of Fos and Fos/TH-immunoreactive neurons in the NTS in the sham, ADX and ADX+B groups, with the highest number of neurons in the ADX animals. Similarly to its effect on food intake, pretreatment with AS30 in the ADX group also reversed the increased activation of NTS neurons induced by refeeding while having no effect in the sham and ADX+B animals. The present results show that adrenalectomy induces an increase in CRF mRNA expression in the PVN potentiated by feeding and that CRF(2) receptor antagonist abolishes the anorexigenic effect and the increased activation of NTS induced by feeding in the ADX animals. These data indicate that increased activity of PVN CRF neurons modulates brainstem satiety-related responses, contributing to hypophagia after adrenalectomy.
Asunto(s)
Adrenalectomía , Hormona Liberadora de Corticotropina/fisiología , Ingestión de Alimentos/genética , Trastornos de Alimentación y de la Ingestión de Alimentos/genética , Respuesta de Saciedad , Adrenalectomía/rehabilitación , Animales , Corticosterona/farmacología , Hormona Liberadora de Corticotropina/genética , Hormona Liberadora de Corticotropina/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Ingestión de Alimentos/efectos de los fármacos , Ingestión de Alimentos/fisiología , Trastornos de Alimentación y de la Ingestión de Alimentos/inducido químicamente , Trastornos de Alimentación y de la Ingestión de Alimentos/metabolismo , Expresión Génica/efectos de los fármacos , Antagonistas de Hormonas/farmacología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/metabolismo , Fragmentos de Péptidos/farmacología , Ratas , Ratas Wistar , Receptores de Hormona Liberadora de Corticotropina/antagonistas & inhibidores , Respuesta de Saciedad/efectos de los fármacos , Respuesta de Saciedad/fisiologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: In folk medicine, Turnera diffusa Wild (Turnera diffusa, Turneraceae) is considered as an aphrodisiac, but its ability to restore copulation in sexually inhibited subjects has not been reported. AIM OF THE STUDY: To determine whether Turnera diffusa recovers sexual behavior in sexually exhausted (SExh) male rats and to identify the main components in an aqueous extract. MATERIALS AND METHODS: SExh males were treated with Turnera diffusa, 20-80 mg/kg, yohimbine, 2 mg/kg, or vehicle. RESULTS: Yohimbine and Turnera diffusa (80 mg/kg) significantly increased the percentage of males achieving one ejaculatory series and resuming a second one. In addition, Turnera diffusa significantly reduced the post-ejaculatory interval. These effects were not associated to an increase in locomotor activity or anxiety-like behaviors. The HPLC-ESI-MS analysis showed the presence of caffeine, arbutine, and flavonoids as the main compounds in the active extract. CONCLUSION: The results support the use of Turnera diffusa as an aphrodisiac in traditional medicine and suggest possible therapeutic properties of Turnera diffusa on sexual dysfunction. The flavonoids present in active extract may participate in its pro-sexual effect, which is analogous to those produced by yohimbine, suggesting a shared mechanism of action.
Asunto(s)
Afrodisíacos/farmacología , Arbutina/farmacología , Cafeína/farmacología , Flavonoides/farmacología , Fitoterapia , Extractos Vegetales/farmacología , Respuesta de Saciedad/efectos de los fármacos , Conducta Sexual Animal/efectos de los fármacos , Turnera , Yohimbina/farmacología , Animales , Femenino , Masculino , Extractos Vegetales/química , Plantas Medicinales/química , Ratas , Ratas Wistar , Turnera/químicaRESUMEN
We investigated the possible role of 5-HT(1A) somatodendritic autoreceptors in the dorsal raphe nucleus (DRN) on salt intake response during basal conditions and following natriorexigenic challenge aroused by sodium depletion in rats. Acute systemic administration (76-1520 nmol/kg s.c.) of 8-OH-DPAT, a selective 5-HT(1A) somatodendritic autoreceptor agonist, induced a clear and dose-dependent preference for salt intake through free choice between water and 0.3 M NaCl simultaneously offered under basal conditions. Acute intra-DRN microinjection (7.5 nmol/rat) of 8-OH-DPAT significantly mimicked the acute systemic protocol in sodium-replete rats. Interestingly, microinjection of 8-OH-DPAT into the DRN raised an additional long-lasting increase of 0.3 M NaCl intake in sodium-depleted rats despite a high volume ingested 30 min after central injection. Conversely, chronic systemic treatment (1520 nmol/kg s.c.) with 8-OH-DPAT for 2 and 3 weeks or repeated intra-DRN microinjection (7.5 nmol/rat) evoked a significant long-term decrease in 0.3 M NaCl intake in sodium-depleted rats given only water and a sodium-deficient diet over the course of 24 h after furosemide injection. These results show a clear-cut involvement of the DRN 5-HT(1A) somatodendritic autoreceptors in sodium satiety signaling under basal conditions and during the consummatory phase of salt intake in sodium-depleted rats.
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Autorreceptores/fisiología , Núcleos del Rafe/metabolismo , Receptor de Serotonina 5-HT1A/metabolismo , Respuesta de Saciedad/fisiología , Cloruro de Sodio Dietético/metabolismo , Equilibrio Hidroelectrolítico/fisiología , 8-Hidroxi-2-(di-n-propilamino)tetralin/farmacología , Animales , Autorreceptores/efectos de los fármacos , Dendritas/efectos de los fármacos , Dendritas/metabolismo , Dendritas/ultraestructura , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo/efectos de los fármacos , Esquema de Medicación , Furosemida/farmacología , Masculino , Microinyecciones , Puente/citología , Puente/efectos de los fármacos , Puente/metabolismo , Núcleos del Rafe/citología , Núcleos del Rafe/efectos de los fármacos , Ratas , Ratas Wistar , Respuesta de Saciedad/efectos de los fármacos , Agonistas del Receptor de Serotonina 5-HT1 , Agonistas de Receptores de Serotonina/farmacología , Cloruro de Sodio/metabolismo , Cloruro de Sodio/farmacología , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico/farmacología , Equilibrio Hidroelectrolítico/efectos de los fármacosRESUMEN
BACKGROUND & AIMS: Syrup obtained from yacon roots could be well positioned as a nutraceutical product due to its high fructooligosaccharides content. We examined the beneficial effects and tolerance of yacon syrup on human health. METHODS: Obese and slightly dyslipidemic pre-menopausal women were studied over a 120-day period in a double-blind placebo-controlled experiment. We used two doses of yacon syrup, 0.29 g and 0.14 g fructooligosaccharides/kg/day. At the start and end of the study, anthropometric measurements, blood glucose, calcium, lipid and insulin concentrations and Homeostasis Model Assessment index were determined. RESULTS: The recommended daily consumption of yacon syrup with no undesirable gastrointestinal effects is 0.14 g fructooligosaccharides/kg. Daily intake of yacon syrup produced a significant decrease in body weight, waist circumference and body mass index. Additionally, decrease in fasting serum insulin and Homeostasis Model Assessment index was observed. The consumption of yacon syrup increased defecation frequency and satiety sensation. Fasting glucose and serum lipids were not affected by syrup treatment and the only positive effect was found in serum LDL-cholesterol levels. CONCLUSIONS: Yacon syrup is a good source of fructooligosaccharides and its long-term consumption produced beneficial health effects on obese pre-menopausal women with insulin resistance.
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Resistencia a la Insulina , Obesidad/dietoterapia , Extractos Vegetales/administración & dosificación , Preparaciones de Plantas/farmacología , Adulto , Antropometría , Glucemia/efectos de los fármacos , Índice de Masa Corporal , Peso Corporal/efectos de los fármacos , Calcio/sangre , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Dislipidemias/dietoterapia , Femenino , Humanos , Insulina/sangre , Lípidos/sangre , Persona de Mediana Edad , Respuesta de Saciedad/efectos de los fármacosRESUMEN
Opioid mechanisms are involved in the control of water and NaCl intake and opioid receptors are present in the lateral parabrachial nucleus (LPBN), a site of important inhibitory mechanisms related to the control of sodium appetite. Therefore, in the present study we investigated the effects of opioid receptor activation in the LPBN on 0.3 M NaCl and water intake in rats. Male Holtzman rats with stainless steel cannulas implanted bilaterally in the LPBN were used. In normohydrated and satiated rats, bilateral injections of the opioid receptor agonist beta-endorphin (2 nmol/0.2 microl) into the LPBN induced 0.3 M NaCl (17.8+/-5.9 vs. saline: 0.9+/-0.5 ml/240 min) and water intake (11.4+/-3.0 vs. saline: 1.0+/-0.4 ml/240 min) in a two-bottle test. Bilateral injections of the opioid antagonist naloxone (100 nmol/0.2 microl) into the LPBN abolished sodium and water intake induced by beta-endorphin into the LPBN and also reduced 0.3 M NaCl intake (12.8+/-1.5 vs. vehicle: 22.4+/-3.1 ml/180 min) induced by 24 h of sodium depletion (produced by the treatment with the diuretic furosemide s.c.+sodium deficient food for 24 h). Bilateral injections of beta-endorphin into the LPBN in satiated rats produced no effect on water or 2% sucrose intake when water alone or simultaneously with 2% sucrose was offered to the animals. The results show that opioid receptor activation in the LPBN induces hypertonic sodium intake in satiated and normohydrated rats, an effect not due to general ingestive behavior facilitation. In addition, sodium depletion induced 0.3 M NaCl intake also partially depends on opioid receptor activation in the LPBN. The results suggest that deactivation of inhibitory mechanisms by opioid receptor activation in the LPBN releases sodium intake if excitatory signals were activated (sodium depletion) or not.
Asunto(s)
Puente/efectos de los fármacos , Puente/fisiología , Receptores Opioides delta/metabolismo , Receptores Opioides mu/metabolismo , Cloruro de Sodio/farmacocinética , betaendorfina/farmacología , Animales , Ingestión de Líquidos/efectos de los fármacos , Ingestión de Líquidos/fisiología , Interacciones Farmacológicas , Encefalina Ala(2)-MeFe(4)-Gli(5)/farmacología , Masculino , Microinyecciones , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Ratas , Ratas Sprague-Dawley , Receptores Opioides delta/antagonistas & inhibidores , Receptores Opioides mu/antagonistas & inhibidores , Respuesta de Saciedad/efectos de los fármacos , Respuesta de Saciedad/fisiología , Sacarosa/farmacología , Agua/metabolismo , betaendorfina/metabolismoRESUMEN
The hypothalamic AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) pathway is known to play an important role in the control of food intake and energy expenditure. Here, we hypothesize that citrate, an intermediate metabolite, activates hypothalamic ACC and is involved in the control of energy mobilization. Initially, we showed that ICV citrate injection decreased food intake and diminished weight gain significantly when compared to control and pair-fed group results. In addition, we showed that intracerebroventricular (ICV) injection of citrate diminished (80% of control) the phosphorylation of ACC, an important AMPK substrate. Furthermore, citrate treatment inhibited (75% of control) hypothalamic AMPK phosphorylation during fasting. In addition to its central effect, ICV citrate injection led to low blood glucose levels during glucose tolerance test (GTT) and high glucose uptake during hyperglycemic-euglycemic clamp. Accordingly, liver glycogen content was higher in animals given citrate (ICV) than in the control group (23.3+/-2.5 vs. 2.7+/-0.5 microg mL(-1) mg(-1), respectively). Interestingly, liver AMPK phosphorylation was reduced (80%) by the citrate treatment. The pharmacological blockade of beta3-adrenergic receptor (SR 59230A) blocked the effect of ICV citrate and citrate plus insulin on liver AMPK phosphorylation. Consistently with these results, rats treated with citrate (ICV) presented improved insulin signal transduction in liver, skeletal muscle, and epididymal fat pad. Similar results were obtained by hypothalamic administration of ARA-A, a competitive inhibitor of AMPK. Our results suggest that the citrate produced by mitochondria may modulate ACC phosphorylation in the hypothalamus, controlling food intake and coordinating a multiorgan network that controls glucose homeostasis and energy uptake through the adrenergic system.
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Acetil-CoA Carboxilasa/metabolismo , Ácido Cítrico/farmacología , Glucosa/metabolismo , Homeostasis/efectos de los fármacos , Hipotálamo/enzimología , Hígado/metabolismo , Respuesta de Saciedad/efectos de los fármacos , Proteínas Quinasas Activadas por AMP , Animales , Peso Corporal/efectos de los fármacos , Ácido Cítrico/administración & dosificación , Corticosterona/sangre , Conducta Alimentaria/efectos de los fármacos , Prueba de Tolerancia a la Glucosa , Glucógeno/metabolismo , Hipotálamo/efectos de los fármacos , Inyecciones Intraventriculares , Insulina/sangre , Hígado/enzimología , Masculino , Complejos Multienzimáticos/metabolismo , Fosforilación/efectos de los fármacos , Propanolaminas , Proteínas Serina-Treonina Quinasas/metabolismo , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacosRESUMEN
Previous studies demonstrated the inhibitory participation of serotonergic (5-HT) and oxytocinergic (OT) neurons on sodium appetite induced by peritoneal dialysis (PD) in rats. The activity of 5-HT neurons increases after PD-induced 2% NaCl intake and decreases after sodium depletion; however, the activity of the OT neurons appears only after PD-induced 2% NaCl intake. To discriminate whether the differential activations of the 5-HT and OT neurons in this model are a consequence of the sodium satiation process or are the result of stimulation caused by the entry to the body of a hypertonic sodium solution during sodium access, we analyzed the number of Fos-5-HT- and Fos-OT-immunoreactive neurons in the dorsal raphe nucleus and the paraventricular nucleus of the hypothalamus-supraoptic nucleus, respectively, after isotonic vs. hypertonic NaCl intake induced by PD. We also studied the OT plasma levels after PD-induced isotonic or hypertonic NaCl intake. Sodium intake induced by PD significantly increased the number of Fos-5-HT cells, independently of the concentration of NaCl consumed. In contrast, the number of Fos-OT neurons increased after hypertonic NaCl intake, in both depleted and non-depleted animals. The OT plasma levels significantly increased only in the PD-induced 2% NaCl intake group in relation to others, showing a synergic effect of both factors. In summary, 5-HT neurons were activated after body sodium status was reestablished, suggesting that this system is activated under conditions of satiety. In terms of the OT system, both OT neural activity and OT plasma levels were increased by the entry of hypertonic NaCl solution during sodium consumption, suggesting that this system is involved in the processing of hyperosmotic signals.
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Neuronas/fisiología , Oxitocina/fisiología , Respuesta de Saciedad/efectos de los fármacos , Serotonina/fisiología , Sodio en la Dieta , Equilibrio Hidroelectrolítico/efectos de los fármacos , Animales , Apetito/efectos de los fármacos , Hipernatremia/fisiopatología , Hipovolemia/fisiopatología , Inmunohistoquímica , Masculino , Neuronas/efectos de los fármacos , Concentración Osmolar , Núcleo Hipotalámico Paraventricular/fisiología , Diálisis Peritoneal , Núcleos del Rafe/fisiología , Ratas , Ratas Wistar , Núcleo Supraóptico/fisiología , Equilibrio Hidroelectrolítico/fisiologíaRESUMEN
Structures of the lamina terminalis (LT) sense and integrate information reflecting the state of body water and sodium content. Output from the LT projects into a neural network that regulates body fluid balance. Serotonin (5-HT) and the dorsal raphe nuclei (DRN) have been implicated in the inhibitory control of salt intake (i.e., sodium appetite). Signals arriving from the LT evoked by fluid depletion-induced sodium ingestion interact with this inhibitory serotonergic system. We investigated the role of neurons along the LT that directly project to the DRN. We analyzed the pattern of immunoreactivity (ir) of LT cells double-labeled for Fos (a marker of neural activity) and Fluorogold (FG; a retrograde tracer) following sodium depletion-induced sodium intake. Seven days after injection of FG into the DRN, sodium appetite was induced by furosemide injection and overnight access to only a low sodium diet (Furo-LSD) and distilled water. Twenty-four hours later, access to 0.3 M NaCl was given to depleted or sham-depleted rats and sodium intake was measured over the following 60 min. Ninety minutes after the termination of the intake test, the animals were perfused and their brains were processed for immunohistochemical detection of Fos and FG. Compared to sham-depleted animals there was a significantly greater number of Fos-/FG-ir double-labeled cells in the subfornical organ, the organum vasculosum of the lamina terminalis and the median preoptic nucleus in rats that ingested NaCl. Projections from the LT cells may contribute to inhibitory mechanisms involving 5-HT neurons in the DRN that limit the intake of sodium and prevent excess volume expansion.
Asunto(s)
Regulación del Apetito/fisiología , Hipotálamo/metabolismo , Vías Nerviosas/metabolismo , Núcleos del Rafe/metabolismo , Cloruro de Sodio Dietético/metabolismo , Equilibrio Hidroelectrolítico/fisiología , Alostasis/efectos de los fármacos , Alostasis/fisiología , Animales , Regulación del Apetito/efectos de los fármacos , Recuento de Células , Diuréticos/farmacología , Alimentos Formulados , Furosemida/farmacología , Hipotálamo/citología , Hipotálamo/efectos de los fármacos , Inmunohistoquímica , Masculino , Vías Nerviosas/citología , Vías Nerviosas/efectos de los fármacos , Área Preóptica/citología , Área Preóptica/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Núcleos del Rafe/citología , Núcleos del Rafe/efectos de los fármacos , Ratas , Ratas Wistar , Respuesta de Saciedad/efectos de los fármacos , Respuesta de Saciedad/fisiología , Cloruro de Sodio Dietético/farmacología , Estilbamidinas , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/fisiología , Equilibrio Hidroelectrolítico/efectos de los fármacosRESUMEN
This study examined the ingestive and behavioral effects of NMDA- and AMPA/kainate glutamatergic receptor blockade in the lateral hypothalamic area (LHy) of free-feeding pigeons (Columba livia). Injections of MK-801 (NMDA receptor antagonist; 6 nmol) or CNQX (AMPA/kainate receptor antagonist; 25.8 nmol) into the LHy of free-feeding pigeons induced significant increases in food intake and in feeding duration, as well as reductions in the latency to start feeding. Duration, latency and volume of water intake, as well as duration of sleep-like behavior, alert immobility, locomotion and preening were not changed by these treatments in the LHy. These results indicate that glutamatergic inputs to cells containing NMDA and/or AMPA receptors located in the LHy could modify both the beginning of a feeding bout (or the end of a period of satiety) and its duration (satiation). Our data also suggest that these inhibitory glutamatergic influences on feeding behavior are tonically active in the LHy.
Asunto(s)
Columbidae/metabolismo , Conducta Alimentaria/fisiología , Ácido Glutámico/metabolismo , Área Hipotalámica Lateral/metabolismo , Neuronas/metabolismo , Receptores de Glutamato/metabolismo , 6-Ciano 7-nitroquinoxalina 2,3-diona/farmacología , Animales , Regulación del Apetito/efectos de los fármacos , Regulación del Apetito/fisiología , Columbidae/anatomía & histología , Maleato de Dizocilpina/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Conducta Alimentaria/efectos de los fármacos , Área Hipotalámica Lateral/anatomía & histología , Área Hipotalámica Lateral/efectos de los fármacos , Masculino , Microinyecciones/métodos , Inhibición Neural/efectos de los fármacos , Inhibición Neural/fisiología , Vías Nerviosas/anatomía & histología , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/metabolismo , Neuronas/efectos de los fármacos , Terminales Presinápticos/efectos de los fármacos , Terminales Presinápticos/metabolismo , Receptores AMPA/antagonistas & inhibidores , Receptores AMPA/metabolismo , Receptores de Glutamato/efectos de los fármacos , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/metabolismo , Respuesta de Saciedad/efectos de los fármacos , Respuesta de Saciedad/fisiología , Especificidad de la Especie , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/fisiologíaRESUMEN
BACKGROUND: Obesity represents a major public health problem in western countries. Initial studies suggest that injection of botulinum A toxin (Btx-A) into the antropyloric region inhibits propulsive contractions of the antral pump, with delay in gastric emptying, early satiety and weight loss. METHODS: After approval by the University Ethics Committee, we prospectively evaluated 12 patients with class III obesity divided into 4 groups of 3 patients each. In groups I and II, 200 U Btx-A were injected into the antropyloric region at 8 and 16 sites, respectively. Groups III and IV received 300 U Btx-A into the antropyloric region at 16 and 24 sites, respectively. Body weight and gastric emptying time (GET) of solids and semi-solids using 13C-octanoic acid breath test and 13C-acetic acid breath test, respectively, were determined before and after injection over a period of 12 weeks. RESULTS: Pre- and post-treatment body weight or solid and semi-solid GET did not differ significantly between groups (P>0.05). All patients reported a feeling of early satiety. No adverse effects related to BtxA or complications resulting from the endoscopic procedure were observed. CONCLUSION: The injection of different doses of BtxA at different sites in the antropyloric region of patients with class III obesity did not interfere significantly with the solid and semi-solid GET or body weight of these individuals. However, early satiety was reported by all patients, the procedure was safe and no side-effects of the treatment were observed. Further controlled studies involving different methodologies regarding dosage of Btx-A and sites of injection are necessary.
Asunto(s)
Toxinas Botulínicas Tipo A/uso terapéutico , Fármacos Neuromusculares/uso terapéutico , Obesidad Mórbida/tratamiento farmacológico , Adolescente , Adulto , Peso Corporal/efectos de los fármacos , Toxinas Botulínicas Tipo A/administración & dosificación , Endoscopía Gastrointestinal , Femenino , Vaciamiento Gástrico/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Fármacos Neuromusculares/administración & dosificación , Proyectos Piloto , Estudios Prospectivos , Respuesta de Saciedad/efectos de los fármacosRESUMEN
Initially used to measure algic symptoms, visual analogue scales (VAS) can also be useful for the evaluation of satiety. The antiobesity agent sibutramine, unlike anorectic agents, decreases food intake mainly by stimulating satiety. To evaluate the effect of sibutramine on satiety, we used a VAS in obese adolescents participating in a double-blind, randomized trial comparing 10 mg of sibutramine to placebo. Each patient received 13 scales to be checked at hourly intervals, in a single day, from 9 am to 9 pm. A 500 kcal deficit diet was divided into 3 meals, with previously fixed times: 9:30 h, 12:30 h, 18:30 h. Using the scores obtained from each scale, a line graph was designed to represent the average satiety score throughout the day. Comparing the area under the curve for the 2 groups, we found 4.609 +/- 1.309 for the group treated with sibutramine and 4.141 +/- 1.432 for the placebo group, not reaching statistical significance (p= NS). Therefore, sibutramine does not seem do have an effect on satiety of obese adolescents, at least when satiety is evaluated by a VAS.
Asunto(s)
Depresores del Apetito/uso terapéutico , Ciclobutanos/uso terapéutico , Obesidad/tratamiento farmacológico , Respuesta de Saciedad/efectos de los fármacos , Adolescente , Depresores del Apetito/farmacología , Ciclobutanos/farmacología , Método Doble Ciego , Femenino , Humanos , Masculino , Respuesta de Saciedad/fisiología , Factores de Tiempo , Pérdida de Peso/efectos de los fármacos , Pesos y MedidasRESUMEN
Copulation to exhaustion induces a sexual inhibitory state featured by a decreased motivation. Since diminished motivation is a key symptom of depression, we analysed if sexually exhausted animals showed increased levels of depressive-like behaviour in the forced swimming test (FST). Besides, sexual activity has been reported to have reinforcing properties. Thus, we analysed whether different levels of sexual activity modified the development of the behavioural despair in the FST. Finally, the effect of a sub-threshold dose of desipramine (DMI, 2.5mg/kg) was evaluated in animals with different sexual conditions. Male adult rats were divided into: (a) naive rats and (b) animals executing one intromission (1-INTR) or (c) one ejaculation (1-EJ) and (d) sexually satiated rats, classified as sexually responsive (R) and non-responsive (NR). No differences were found in immobility behaviour between sexually exhausted and naive rats. In the pre-test sessions of the FST males attaining ejaculation (1-EJ, R and NR) had lower levels of immobility or showed a tendency towards such a diminution, while animals with sexual activity not involving ejaculation did not. Data suggest a "protective" effect of ejaculation against the development of depressive-like behaviour. Finally, the sub-effective dose of DMI produced an antidepressant-like action in all animals that ejaculated. In conclusion, sexual experience involving ejaculation modifies the behavioural expression of rats in the FST and their sensitivity to antidepressant drugs like DMI. Both responses reflect brain plastic changes induced by ejaculation.
Asunto(s)
Antidepresivos Tricíclicos/farmacología , Conducta Animal/efectos de los fármacos , Desipramina/farmacología , Eyaculación/fisiología , Natación/psicología , Análisis de Varianza , Animales , Conducta Animal/fisiología , Depresión/tratamiento farmacológico , Depresión/psicología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Eyaculación/efectos de los fármacos , Pérdida de Tono Postural/efectos de los fármacos , Masculino , Actividad Motora/efectos de los fármacos , Ratas , Respuesta de Saciedad/efectos de los fármacos , Respuesta de Saciedad/fisiología , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
Inicialmente empregadas para mensuracão de sintomas álgicos, as escalas visuais analógicas (EVAs) podem ser também um instrumento útil para avaliacão da saciedade. O agente antiobesidade sibutramina, ao contrário dos anorexígenos, parece exercer seu efeito de reducão de ingestão alimentar principalmente por estímulo da saciedade. Com o objetivo de avaliar o efeito da sibutramina sobre a saciedade, utilizamos uma EVA em adolescentes obesos que participaram de um estudo duplo-cego randomizado, comparando sibutramina 10mg com placebo. Cada paciente recebeu 13 escalas para serem preenchidas em intervalos de uma hora, num único dia, das 9 às 21h. Uma dieta com déficit de 500kcal diárias foi dividida em 3 refeicões, com horários previamente estipulados: 9:30h, 12:30h, 18:30h. A partir da pontuacão obtida em cada uma das escalas, construiu-se um gráfico de linha representativo da pontuacão média de saciedade ao longo do dia. Comparando-se a área sob a curva dos 2 grupos, encontramos 4.609 n 1.309 para o grupo tratado com sibutramina e 4.141 n 1.432 para o grupo placebo (p= NS). Desta forma, a sibutramina não parece apresentar efeito sobre a saciedade de adolescentes obesos, pelo menos quando avaliado através de uma EVA.
Asunto(s)
Adolescente , Humanos , Masculino , Femenino , Depresores del Apetito/uso terapéutico , Ciclobutanos/uso terapéutico , Obesidad/tratamiento farmacológico , Dimensión del Dolor/métodos , Respuesta de Saciedad/efectos de los fármacos , Depresores del Apetito/farmacología , Ciclobutanos/farmacología , Método Doble Ciego , Respuesta de Saciedad/fisiología , Factores de Tiempo , Pérdida de Peso/efectos de los fármacosRESUMEN
The present article reviews the current findings on the interesting phenomenon of sexual satiety. Knut Larsson in 1956 reported on the development of sexual exhaustion in the male rat after repeated copulation. We have studied the process and found the following results. (1) One day after 4 hours of ad libitum copulation, two-thirds of the population showed complete inhibition of sexual behavior, while the other third displayed a single ejaculatory series from which they did not recover. (2) Several pharmacological treatments, including 8-OH-DPAT, yohimbine, naloxone and naltrexone, reverse this sexual satiety, indicating that the noradrenergic, serotonergic and opiate systems are involved in this process. Indeed, direct neurochemical determinations showed changes in various neurotransmitters during sexual exhaustion. (3) Given enough stimulation, by changing the stimulus female, sexual satiety was prevented, suggesting that there are motivational components of the sexual inhibition that characterizes sexual exhaustion. (4) The GABA antagonist bicuculline, or the electrical stimulation of the medial preoptic area, did not reverse sexual exhaustion. These data suggest, on the one hand, that sexual exhaustion and the postejaculatory interval (which is shortened by bicuculline administration) are not mediated by similar mechanisms and, on the other, that the medial preoptic area does not regulate sexual satiety. (5) The androgen receptor density in brain areas closely related to the expression of masculine sexual behavior, such as the medial preoptic nucleus, was drastically reduced in sexually exhausted animals. Such reduction was specific to certain brain areas and was not related to changes in the levels of androgens. These results suggest that changes in brain androgen receptors account for the inhibition of sexual behavior present during sexual exhaustion. (6) The recovery process of sexual satiety after 4 hours of ad libitum copulation reveals that, after 4 days, only 63% of the males are able to show sexual behavior while after 7 days all animals display copulatory activity.