RESUMO
Exercise promotes resilience to stress and increases galanin in the locus coeruleus (LC), but the question of whether changes in galanin signaling mediate the stress-buffering effects of exercise has never been addressed. To test the contributions of galanin to stress resilience, male Sprague Dawley rats received intracerebroventricular (ICV) cannulation for drug delivery and frontocortical cannulation for microdialysis, and were housed with or without a running wheel for 21d. Rats were acutely injected with vehicle or the galanin receptor antagonist M40 and exposed to a single session of either footshock or no stress. Other groups received galanin, the galanin receptor antagonist M40, or vehicle chronically for 21d prior to the stress session. Microdialysis sampling occurred during stress exposure and anxiety-related behavior was measured on the following day in the elevated plus maze. Dendritic spines were visualized by Golgi impregnation in medial prefrontal cortex (mPFC) pyramidal neurons and quantified. Exercise increased galanin levels in the LC. Under non-stressed conditions, anxiety-related behavior and dopamine levels were comparable between exercised and sedentary rats. In contrast, exposure to stress reduced open arm exploration in sedentary rats but not in exercise rats or those treated chronically with ICV galanin, indicating improved resilience. Both exercise and chronic, ICV galanin prevented the increased dopamine overflow and loss of dendritic spines observed after stress in sedentary rats. Chronic, but not acute M40 administration blocked the resilience-promoting effects of exercise. The results indicate that increased galanin levels promote features of resilience at both behavioral and neural levels.
Assuntos
Encéfalo/patologia , Galanina/metabolismo , Neurônios/metabolismo , Condicionamento Físico Animal/métodos , Estresse Psicológico/patologia , Estresse Psicológico/reabilitação , Animais , Ansiedade/patologia , Ansiedade/reabilitação , Encéfalo/metabolismo , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Eletrochoque/efeitos adversos , Ensaio de Imunoadsorção Enzimática , Comportamento Exploratório/efeitos dos fármacos , Galanina/administração & dosagem , Galanina/agonistas , Galanina/análogos & derivados , Infusões Intraventriculares , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Microdiálise , Neurônios/ultraestrutura , Fragmentos de Peptídeos/administração & dosagem , Ratos , Ratos Sprague-Dawley , Coloração pela Prata , Estresse Psicológico/etiologiaRESUMO
Use of 5-fluoropyridimine antimetabolite drugs, specifically 5-fluorouracil (5-FU), has been discouraged in cats because of adverse events including neurotoxicity and death. Causes of toxicity have never been elucidated. In humans, toxicity has been associated with ineffective metabolism secondary to deficiencies in dihydropyrimidine dehydrogenase (DPD). Direct assessment of DPD activity is challenging; determination of uracil:dihydrouracil (U:UH2 ) in plasma using high performance liquid chromatography (HPLC) has been reported as an indirect measurement. U:UH2 was measured in the plasma of 73 cats. Mean U:UH2 for all cats was 1.66 ± 0.11 (median 1.53, range 0.24-7.00). Seventeen (23%) cats had U:UH2 >2, a value associated with decreased DPD activity in humans. Spayed female cats had significantly lower U:UH2 as compared with intact females, and age and U:UH2 were weakly but significantly negatively correlated (r = -0.26). Studies correlating U:UH2 and 5-FU tolerability are required to further determine the validity and use of this test in cats.
Assuntos
Doenças do Gato/induzido quimicamente , Di-Hidrouracila Desidrogenase (NADP)/metabolismo , Fluoruracila/efeitos adversos , Uracila/análogos & derivados , Uracila/sangue , Envelhecimento , Animais , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/metabolismo , Gatos , Di-Hidrouracila Desidrogenase (NADP)/genética , Feminino , Fluoruracila/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Masculino , Uracila/metabolismoRESUMO
Although Parkinson's disease (PD) is characterized primarily by loss of nigrostriatal dopaminergic neurons, there is a concomitant loss of norepinephrine (NE) neurons in the locus coeruleus. Dopaminergic lesions induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are commonly used to model PD, and although MPTP effectively mimics the dopaminergic neuropathology of PD in mice, it fails to produce PD-like motor deficits. We hypothesized that MPTP is unable to recapitulate the motor abnormalities of PD either because the behavioral paradigms used to measure coordinated behavior in mice are not sensitive enough or because MPTP in the absence of NE loss is insufficient to impair motor control. We tested both possibilities by developing a battery of coordinated movement tests and examining motor deficits in dopamine beta-hydroxylase knockout (Dbh-/-) mice that lack NE altogether. We detected no motor abnormalities in MPTP-treated control mice, despite an 80% loss of striatal dopamine (DA) terminals. Dbh-/- mice, on the other hand, were impaired in most tests and also displayed spontaneous dyskinesias, despite their normal striatal DA content. A subset of these impairments was recapitulated in control mice with 80% NE lesions and reversed in Dbh-/- mice, either by restoration of NE or treatment with a DA agonist. MPTP did not exacerbate baseline motor deficits in Dbh-/- mice. Finally, striatal levels of phospho-ERK-1/2 and DeltaFosB/FosB, proteins which are associated with PD and dyskinesias, were elevated in Dbh-/- mice. These results suggest that loss of locus coeruleus neurons contributes to motor dysfunction in PD.
Assuntos
1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Atividade Motora/efeitos dos fármacos , Norepinefrina/metabolismo , Animais , Comportamento Animal , Dopamina beta-Hidroxilase/deficiência , Dopamina beta-Hidroxilase/genética , Dopamina beta-Hidroxilase/metabolismo , Locus Cerúleo/metabolismo , Camundongos , Camundongos Knockout , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fenótipo , Fosforilação , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Receptores Dopaminérgicos/metabolismoAssuntos
Sistema X-AG de Transporte de Aminoácidos/biossíntese , Tonsila do Cerebelo/metabolismo , Aprendizagem da Esquiva/efeitos dos fármacos , Cocaína/farmacologia , Receptores de Glutamato/biossíntese , Paladar/efeitos dos fármacos , Paladar/genética , Sistema X-AG de Transporte de Aminoácidos/genética , Animais , Resistência a Medicamentos , Expressão Gênica/efeitos dos fármacos , Ratos , Receptores de Glutamato/genética , Especificidade da EspécieAssuntos
Tonsila do Cerebelo/metabolismo , Aprendizagem da Esquiva/efeitos dos fármacos , Proteínas Quinases Dependentes de Cálcio-Calmodulina/biossíntese , Cocaína/farmacologia , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/fisiologia , Paladar/efeitos dos fármacos , Paladar/genética , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/enzimologia , Animais , Proteínas Quinases Dependentes de Cálcio-Calmodulina/genética , Proteína 4 Homóloga a Disks-Large , Resistência a Medicamentos , Expressão Gênica/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular , Proteínas de Membrana , Proteínas do Tecido Nervoso/genética , Ratos , Ratos Sprague-Dawley , Proteínas Associadas SAP90-PSD95RESUMO
The effects of neurotoxic destruction of catecholaminergic projections to the spinal cord on cannabinoid antinociception were examined in models of acute and tonic nociception. High performance liquid chromatography was used to quantify monoamine levels in sham-operated and lesioned rats. Intrathecal administration of the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA) induced a selective depletion of norepinephrine (by approximately 85% of control) in rat lumbar spinal cord without altering levels of dopamine or serotonin. By contrast, brain levels of monoamines did not differ in sham-operated and lesioned rats. Pain behavior was similar in sham-operated and lesioned rats receiving vehicle in models of both acute and tonic nociception. The cannabinoid agonist WIN55,212-2 (5 or 10 mg/kg, i.p.) produced antinociception in the tail-flick test in sham-operated rats. The antinociceptive effect of WIN55,212-2 was attenuated relative to control conditions in rats depleted of spinal norepinephrine. WIN55,212-2 suppressed tonic pain behavior in the formalin test in sham-operated rats during phase 2 (15-60 min post formalin) of nociceptive responding. By contrast, in lesioned rats, WIN55,212-2 suppressed pain behavior during phase 1 (0-9.9 min) and phase 2A (10-39.9 min), but not during phase 2B (40-60 min). The cannabinoid agonist suppressed formalin-evoked Fos protein expression, a marker of neuronal activity, in the lumbar dorsal horn of sham-operated rats, but no suppression was observed in lesioned rats. The number of formalin-evoked Fos-like immunoreactive (FLI) cells was greater in lamina I and II of lesioned rats relative to sham-operated rats. These data indicate that the suppressive effect of the cannabinoid on formalin-evoked Fos protein expression in the superficial dorsal horn was attenuated following destruction of descending noradrenergic pathways. Our data are consistent with the hypothesis that cannabinoids produce antinociception, in part, by modulating descending noradrenergic systems and support a differential involvement of noradrenergic projections to the spinal cord in cannabinoid modulation of acute versus tonic nociception.
Assuntos
Canabinoides/farmacologia , Modelos Animais de Doenças , Norepinefrina/metabolismo , Oxidopamina/toxicidade , Medição da Dor/efeitos dos fármacos , Analgésicos/farmacologia , Animais , Benzoxazinas , Masculino , Morfolinas/farmacologia , Naftalenos/farmacologia , Vias Neurais/efeitos dos fármacos , Vias Neurais/fisiologia , Medição da Dor/métodos , Ratos , Ratos Sprague-Dawley , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismoRESUMO
Rats treated with somatotropin (STH) and allowed to self-select between diets varying in protein content will consume more of the high-protein diet. The objective of this study was to determine the role of the hepatic vagus nerve in this ability to select protein. Female Sprague-Dawley rats (n=40) received a hepatic vagotomy (HVAGX) or a sham surgery. Postsurgery, the rats were maintained on pelleted diets for 2 weeks, after which the rats were adapted to selecting between powdered diets with 5% casein and 30% casein. After a 7-day adaptation to diet selection, rats in each surgical treatment group were treated with STH (4 mg/day) or physiological saline for 14 days. Body weight and intake were recorded daily. STH treatment increased growth rate to a similar degree in both sham and HVAGX groups. Despite causing an increase in total food intake, there was no effect of HVAGX alone on body weight. Relative to the sham-saline group, sham-STH in treated rats had greater total food intake that was accounted for entirely by increased consumption of the 30% protein diet and no change in intake of the 5% diet. In contrast, HVAGX+STH rats exhibited 20-30% increases in consumption of both the 5% and 30% protein diets. Thus, the HVAGX+STH rats recognized an increased need for protein, but were unable to distinguish between the high- and low-protein diets and selected more of both. The data suggest that the ability to alter diet selection in response to a stimulation of protein accretion is at least partially mediated through the liver and hepatic branch of the vagus nerve.
Assuntos
Proteínas Alimentares/farmacologia , Preferências Alimentares/efeitos dos fármacos , Preferências Alimentares/fisiologia , Hormônio do Crescimento/farmacologia , Fígado/inervação , Vagotomia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/fisiologia , Aminoácidos/sangue , Animais , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Dieta , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Feminino , Tamanho do Órgão/efeitos dos fármacos , Tamanho do Órgão/fisiologia , Ratos , Ratos Sprague-DawleyRESUMO
This study was undertaken to determine whether casein, compared with its constituent amino acids, given at the onset of a meal, would influence intake due to cholecystokinin (CCK) or opioid activity. Male Sprague-Dawley rats (n = 80; 225 g) were given either premeal loads of casein or its constituent amino acids and treated with opioid or CCK antagonists in a 2 x 4 factorially designed experiment. During a 21-d period, rats were meal-fed by restricting access to food to 5 h/d. The rats were fed the AIN-93 diet with soy isolate substituted for casein as the dietary protein source. On d 7-21, rats were given oral premeal loads of 5 mL of a 50 g/L casein or constituent amino acid solution before meal-feeding. On d 14-21, 20 rats were injected intraperitoneally with one of the following treatments: saline, naltrexone (l mg/kg), naloxone methiodide (5 mg/kg) or lorglumide (1 mg/kg) before the premeal load and feeding. Antagonist treatments increased intake (P < 0.05) by 15.3% compared with saline treatment (7.82 vs. 9.02 g/d) in rats given premeal loads of casein. Intake of rats given premeal loads of amino acids was not influenced by antagonists. At 2 h after feeding on d 21, the rats were killed, bled and eviscerated. Effects of antagonists on stomach and intestinal mass, digesta contents and fecal output were also dependent on the type of premeal load, indicating that gastric retention of digesta due to casein was mediated by CCK and opioids. Body weight accretion, liver, and epididymal fat mass and blood concentrations of specific amino acids changed in the same manner as intake (P < 0.05). Serum insulin was greater (P < 0.05) in casein-treated rats and reduced (P < 0.01) by opioid antagonists. Satiety associated with premeal loads of casein is related to changes in gastrointestinal function of meal-fed animals and involves both opioid and CCK regulation.
Assuntos
Caseínas/farmacologia , Colecistocinina/antagonistas & inibidores , Ingestão de Alimentos/efeitos dos fármacos , Naloxona/análogos & derivados , Antagonistas de Entorpecentes/farmacologia , Proglumida/análogos & derivados , Estômago/fisiologia , Aminoácidos/administração & dosagem , Animais , Glicemia/análise , Caseínas/administração & dosagem , Dieta , Proteínas Alimentares/administração & dosagem , Fezes , Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Intestinos/anatomia & histologia , Intestinos/efeitos dos fármacos , Masculino , Naloxona/farmacologia , Naltrexona/farmacologia , Proglumida/farmacologia , Compostos de Amônio Quaternário , Ratos , Ratos Sprague-Dawley , Proteínas de Soja/administração & dosagem , Estômago/anatomia & histologia , Estômago/efeitos dos fármacosRESUMO
Previous experiments have reported increased seizure susceptibility in transgenic mice lacking normal neuropeptide-Y (NPY) gene expression (i.e. NPY 'knock-out' mice). A critical issue inherent in such experiments concerns the confounding of developmental influences of NPY and its neurotransmitter functions in the mature organism. The present experiments directly addressed this issue by studying seizure susceptibility in transgenic mice possessing an inducible antisense transcript that can be experimentally manipulated to attenuate NPY synthesis. NPY-deficient and control mice were injected with kainic acid (40 mg/kg, i.p.) and several seizure-related behaviors were measured. Consistent with previously reported effects in NPY knock-out mice, significantly more NPY-deficient mice died within 24 h than control mice. In situ hybridization analyses confirmed a decrease in prepro-NPY gene expression in transgenic mice. The experiments support the hypothesis that the control of neural excitability is a prominent function of NPY.
Assuntos
Neuropeptídeo Y/deficiência , Neuropeptídeo Y/genética , Convulsões/mortalidade , Convulsões/fisiopatologia , Animais , Feminino , Regulação da Expressão Gênica/fisiologia , Hipocampo/patologia , Hipocampo/fisiopatologia , Ácido Caínico/efeitos adversos , Masculino , Camundongos , Camundongos Transgênicos , Neurônios/metabolismo , Neurônios/patologia , RNA Mensageiro/metabolismo , Convulsões/induzido quimicamenteRESUMO
We used chemical sympathectomy by 6-hydroxydopamine (6-OHDA) to examine whether adaptation by the sympathetic nervous system (SNS) is a plausible explanation for our prior finding that activity-wheel running blunts the suppression of splenic natural killer cell cytotoxicity after footshock. Male Fischer rats were assigned to treatments using a group (activity wheel vs. sedentary)x treatment (6-OHDA vs. saline)x condition (footshock vs. no shock) design. After 5-6 weeks, rats were injected i.p. with saline or with 40, 80, and 80 mg/kg 6-OHDA on pre experimental days -5, -3, and -1. Half the rats received 6 min of random footshock during a 40-min period. Cytotoxicity was determined by standard 4-h 51Cr release assay. Sympathectomy reduced splenic [NE] by 72%. After 6-OHDA injection and footshock, percent lysis was 33% lower in sedentary rats compared with activity-wheel runners and home-cage controls, p=0.048. The results suggest that activity-wheel running leads to adaptations that offset an altered SNS modulation of splenic NK cell cytotoxicity in response to footshock.
Assuntos
Citotoxicidade Imunológica/fisiologia , Eletrochoque , Pé , Células Matadoras Naturais/fisiologia , Atividade Motora/fisiologia , Baço/fisiologia , Simpatectomia , Animais , Peso Corporal , Norepinefrina/metabolismo , Ratos , Ratos Endogâmicos F344RESUMO
Effects of physical activity on brain noradrenergic response to footshock were examined. Male Fischer 344 rats were randomly assigned to shoebox cages with (AW) or without (SED) 24-hr access to an activity wheel for 4-5 weeks. Extracellular levels of norepinephrine (NE) and 3,4-dihydroxyphenyl-acetic acid (DOPAC) in the brain frontal cortex were measured in 20-min samples of microdialysate taken during a 2-hr baseline, 40 min of scrambled footshock, and a 1-hr recovery. Levels of messenger RNA (mRNA) for tyrosine hydroxylase (TH), c-fos, and prepro-galanin in the locus coeruleus were measured by in situ hybridization histochemistry with autoradiographic analysis. NE levels were the same for SED and AW rats at baseline but were elevated in SED compared with AW during and after footshock. Levels of mRNA for TH and c-fos were elevated after footshock but did not differ between SED and AW. Our findings suggest that wheel running blunts NE release in the brain frontal cortex in response to footshock but does not influence expression of the gene that encodes TH in the locus coeruleus.
Assuntos
Adaptação Psicológica/fisiologia , Eletrochoque , Lobo Frontal/metabolismo , Galanina/metabolismo , Genes fos , Locus Cerúleo/metabolismo , Norepinefrina/biossíntese , Esforço Físico/fisiologia , Tirosina 3-Mono-Oxigenase/metabolismo , Ácido 3,4-Di-Hidroxifenilacético/análise , Animais , Autorradiografia , Condicionamento Operante , Pé , Lobo Frontal/cirurgia , Galanina/genética , Genes fos/genética , Hibridização In Situ , Masculino , RNA Mensageiro/análise , Distribuição Aleatória , Ratos , Ratos Endogâmicos F344 , Tirosina 3-Mono-Oxigenase/genéticaRESUMO
Ingestion of food and fluid stimulates release of a number of peptides from the gastrointestinal system. These peptides are recognized to act as neurotransmitters/neuromodulators and act at both peripheral and central receptors. Many studies indicate that these peptides are important signals in terminating meals. Recent studies suggest that bombesin, a peptide related to gastrin-releasing peptide, suppresses sodium appetite. We have investigated the role of cholecystokinin (CCK) in the control of sodium appetite. Our studies indicate that CCK is effective at reducing saline intake. We found that exogenous, intraperitoneal CCK octapeptide suppresses saline intake. Moreover, administration of trypsin inhibitor to stimulate endogenous CCK release resulted in suppression of saline intake. Finally, intraperitoneal administration of the CCK receptor antagonist lorglumide resulted in increased saline intake. These observations extend the potential role of gastrointestinal peptides in the modulation of ingestive behavior.
Assuntos
Apetite/fisiologia , Bombesina/farmacologia , Encéfalo/fisiologia , Colecistocinina/fisiologia , Fenômenos Fisiológicos do Sistema Digestório , Sódio na Dieta , Animais , Apetite/efeitos dos fármacos , Captopril/farmacologia , Colecistocinina/farmacologia , Furosemida/farmacologia , Antagonistas de Hormônios/farmacologia , Proglumida/análogos & derivados , Proglumida/farmacologia , Receptores da Colecistocinina/antagonistas & inibidores , Sincalida/farmacologiaRESUMO
This study investigated the frequency of mild or asymptomatic measles infections among 44 persons exposed to a student with measles during a 3-day bus trip using two buses. Questionnaires and serum samples were obtained 26-37 days after the trip. All participants had detectable measles-neutralizing antibodies, and none developed classic measles symptoms. Ten persons (23%) were IgM positive for measles, indicating recent infection. Among previously vaccinated IgM-negative persons, those who rode on bus A with the index case-patient had significantly higher microneutralization titers than those on bus B (P= .001), suggesting that some persons on bus A were infected but were IgM negative at the time of the study. Mild or asymptomatic measles infections are probably very common among measles-immune persons exposed to measles cases and may be the most common manifestation of measles during outbreaks in highly immune populations.
Assuntos
Vacina contra Sarampo/imunologia , Vírus do Sarampo/imunologia , Sarampo/epidemiologia , Sarampo/imunologia , Adolescente , Adulto , Idoso , Anticorpos Antivirais/sangue , Surtos de Doenças , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Sarampo/patologia , Pessoa de Meia-IdadeRESUMO
2-Deoxy-d-glucose (2DG) is a glucose analogue that inhibits intracellular utilization of glucose and produces a characteristic behavioral response known as glucoprivic feeding. The area postrema (AP) is a caudal hindbrain structure shown previously to be involved in 2DG-induced glucoprivic feeding. In addition, peripheral administration of 2DG is known to elicit activation of both the hypothalamic-pituitary-adrenal (HPA) axis and the sympathoadrenomedullary system. The neural substrates for these neuroendocrine and neural responses to 2DG are not known although they may also involve the AP. The possible role of the AP in 2DG-induced feeding, activation of the HPA axis and hyperglycemia was investigated in Sprague-Dawley rats with lesions centered on the area postrema (APX) and sham-operated (SHM) rats administered 2DG (200 mg/kg) or physiological saline (1 ml/kg). Peripheral administration of 2DG evoked a feeding response in SHM rats that was abolished in APX animals. Interestingly, 2DG administered at this dose produced a significant increase in plasma corticosterone and plasma glucose in both SHM and APX rats for up to 4 h after drug treatment. Collectively, these findings suggest that the AP is involved in the behavioral (feeding) response to peripheral administration of 2DG, but does not appear to be a common neural substrate for the neuroendocrine (HPA axis) and sympathoadrenal (hyperglycemic) responses to this agent.
Assuntos
Glicemia/efeitos dos fármacos , Desoxiglucose/farmacologia , Comportamento Alimentar/efeitos dos fármacos , Comportamento Alimentar/fisiologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Rombencéfalo/efeitos dos fármacos , Rombencéfalo/fisiologia , Animais , Corticosterona/sangue , Ingestão de Alimentos/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Rombencéfalo/patologia , Núcleo Solitário/efeitos dos fármacos , Núcleo Solitário/fisiologiaRESUMO
Intracerebroventricular (icv) injection of glucagon-like peptide-1 (7-36) amide (GLP-1) has been shown to reduce food intake in rats. In these studies, we confirmed that injection of 10 microg of GLP-1 into the third cerebroventricle suppressed food intake. Moreover, we observed a reduction in water intake associated with the decreased food intake. We further examined whether GLP-1 injected icv in rats has a specific inhibitory effect on water intake. It was found that GLP-1 reduced water deprivation-induced drinking. Furthermore, the same dose of GLP-1 (10 microg) was sufficient to condition taste aversion. Finally, when 2 microg of GLP-1 were injected into the third ventricle, it only suppressed water deprivation-induced water intake and failed to influence spontaneous food and water intakes or induce conditioned taste aversion. These observations indicate that GLP-1 is a potent inhibitor of water intake in the rat and may play a role in the control of fluid homeostasis.
Assuntos
Ventrículos Cerebrais/efeitos dos fármacos , Ingestão de Líquidos/efeitos dos fármacos , Glucagon/farmacologia , Fragmentos de Peptídeos/farmacologia , Precursores de Proteínas/farmacologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Glucagon/administração & dosagem , Peptídeo 1 Semelhante ao Glucagon , Injeções Intraventriculares , Masculino , Fragmentos de Peptídeos/administração & dosagem , Precursores de Proteínas/administração & dosagem , Ratos , Ratos Sprague-Dawley , Paladar/fisiologia , Privação de Água/fisiologiaRESUMO
Our previous work indicates that type and level of dietary fat influences selection of protein and carbohydrate diets. Serotonin (5HT) appears to be involved in this feeding behavior. In the present study, we examined the effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on feeding behavior, and fenfluramine on in vitro 5HT and 5-hydroxyindoleacetic acid (5HIAA) release from the brain in rats fed tallow or corn oil. Male, Sprague-Dawley rats were given a diet containing corn oil or tallow for 2 days. In Experiment 1, rats received an injection of 8-OH-DPAT (a 5HT1A agonist) or saline and were then allowed to select from two diets: low protein/high carbohydrate or high protein/low carbohydrate. Prior exposure to tallow caused an increased intake of protein and 8-OH-DPAT blunted this effect. In Experiment 2, the dorsal raphe from rats fed tallow or corn oil was superfused with fenfluramine or vehicle. Superfusates were collected for analysis of 5HT and 5HIAA. Fenfluramine increased serotonin release in tallow-fed animals as compared to basal. These results suggest that serotonin may be involved in mediating tallow's effect on macronutrient selection.
Assuntos
8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Gorduras na Dieta/farmacologia , Proteínas Alimentares/administração & dosagem , Preferências Alimentares/efeitos dos fármacos , Agonistas do Receptor de Serotonina/farmacologia , Serotonina/fisiologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Óleo de Milho , Gorduras , Fenfluramina/farmacologia , Ácido Hidroxi-Indolacético/metabolismo , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
2-deoxy-D-glucose (2-DG) has been shown to induce increased feeding responses in animals. Recent studies suggest the possible involvement of neuropeptide Y (NPY) in 2-DG-induced feeding. The present study examined the effect of immunoneutralization of endogenous NPY on 2-DG-induced feeding. NPY antibody injected into the paraventricular nucleus of the rats significantly attenuated 2-DG-induced feeding, suggesting that hypothalamic NPY may mediate, at least partly, the effect of 2-DG on food intake.
Assuntos
Desoxiglucose/farmacologia , Comportamento Alimentar/efeitos dos fármacos , Neuropeptídeo Y/imunologia , Animais , Desoxiglucose/imunologia , Soros Imunes , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
5-Thioglucose (5-TG) has been shown to increase food intake after acute administration. To determine the longer-term effects of 5-TG on feeding and body composition, thirty-four female Sprague-Dawley rats were cannulated into the fourth ventricle and infused with artificial CSF and either 0.01 M 5-TG or 0.1 M 5-TG using osmotic pumps. Food intake and body weight were monitored daily. Rats were killed after 14 days of infusion. Carcass and fatpad weights were measured, and body compositions were determined. Food intake was not different during the first week of infusion; however, cumulative food intake was decreased in the 0.1 M 5-TG group during the second week as compared to the CSF control group. Body weight and carcass weight of this group also decreased as compared to the control. The group receiving the higher dose of 5-TG (0.1 M) had increased fatpad weights in all three depots examined (inguinal, retroperitoneal, and perimetrial depot); the group with lower dose of 5-TG infusion (0.01 M) increased the fatpad weights in the retroperitoneal and perimetrial depot, as compared to the CSF group. Data from the body composition analysis were consistent with the results of the fatpad weights. In conclusion, the present study demonstrated that chronic fourth ventricular 5-TG infusion increased body fat without increasing food intake, suggesting that energy expenditure is decreased under this condition. The results of this study indicate that glucose metabolism in the hindbrain is important in the control of energy expenditure, body fat deposition, and thus energy balance regulation.