RESUMO
OBJECTIVE: The natural selective estrogen receptor modulator DT56a (Femarelle), derived from soybean, has been shown to relieve menopausal vasomotor symptoms with no effect on sex steroid hormone levels or endometrial thickness.The purpose of the present study was to evaluate the neuroendocrine effect of DT56a administration through the evaluation of brain content of allopregnanolone (AP), an endogenous neurosteroid gamma-aminobutyric acid agonist with anxiolytic properties, and through the assessment of beta-endorphin (beta-END), the endogenous opioid implicated in pain mechanism, emotional state, and autonomic control. METHODS: Five groups of Wistar ovariectomized (OVX) rats received one of the following treatments: oral DT56a administration at doses of 6, 12, 60, and 120 mg kg(-1) day(-1) or estradiol valerate (E2V) at a dose of 0.05 mg kg(-1) day(-1) for 14 days. One group of fertile and one group of OVX rats receiving placebo were used as controls. The concentration of AP was assessed in the frontal and parietal cortex, hippocampus, hypothalamus, anterior pituitary, and serum, whereas the content of beta-END was evaluated in the frontal and parietal cortex, hippocampus, hypothalamus, neurointermediate lobe, anterior pituitary, and plasma. RESULTS: DT56a increased AP levels in all brain areas analyzed and in serum, with a classical dose-related curve in comparison with OVX rats. In some brain areas, such as the frontal cortex, the parietal cortex, and the anterior pituitary, positive results were found even with the administration of a lower DT56a dose of 60 mg kg(-1) day(-1), attaining AP levels in the range of those in animals treated with E2V. Similarly, beta-END levels were enhanced in selected brain areas such as the hippocampus, the hypothalamus, the neurointermediate lobe, and the anterior pituitary in comparison with those in OVX rats, in which the increase of the opioid was dose related and in the range of those in rats treated with E2V. CONCLUSIONS: This study demonstrated that DT56a positively affects brain neurosteroidogenesis and the opiatergic system: DT56a exerts an estrogen-like effect on selective areas related to mood, cognition, and homeostasis control, presenting a specific pattern of interaction with the brain function. These findings may, in part, explain the clinical effect of DT56a on menopausal symptoms.
Assuntos
Química Encefálica/efeitos dos fármacos , Menopausa , Ovariectomia , Extratos Vegetais/administração & dosagem , Pregnanolona/análise , beta-Endorfina/análise , Administração Oral , Análise de Variância , Animais , Química Encefálica/fisiologia , Córtex Cerebral/química , Córtex Cerebral/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Estradiol/administração & dosagem , Estradiol/análogos & derivados , Estradiol/farmacologia , Terapia de Reposição de Estrogênios/métodos , Feminino , Fogachos/tratamento farmacológico , Fogachos/etiologia , Menopausa/efeitos dos fármacos , Menopausa/fisiologia , Sistemas Neurossecretores/química , Sistemas Neurossecretores/efeitos dos fármacos , Fitoterapia/métodos , Extratos Vegetais/farmacologia , Pregnanolona/fisiologia , Ratos , Ratos Wistar , beta-Endorfina/efeitos dos fármacos , beta-Endorfina/fisiologiaRESUMO
We investigated the plasma glucose-lowering mechanism(s) of Rh2, a ginsenoside derived from Panax ginseng, in rats with streptozotocin-induced diabetes (STZ-diabetic rats). After intravenous injection over 120 min into fasting STZ-diabetic rats, Rh2 decreased plasma glucose in a dose-dependent manner. In parallel to the lowering of plasma glucose, an increase of plasma beta-endorphin-like immunoreactivity was observed. In addition, naloxone and naloxonazine at doses sufficient to block opioid mu-receptors inhibited the plasma glucose-lowering action of Rh2 in genetically wild-type, diabetic mice. In contrast, Rh2 failed to lower plasma glucose in opioid mu-receptor knockout diabetic mice. An increase in gene expression at both the mRNA and protein levels of glucose transporter subtype 4 (GLUT 4) was observed in soleus muscle obtained from STZ-diabetic rats treated with Rh2 three times daily for one day; this increase in expression was absent when opioid mu-receptors were blocked. In conclusion, our results suggest that ginsenoside Rh2 may lower plasma glucose in STZ-diabetic rats based on an increase in beta-endorphin secretion that activates opioid mu-receptors thereby resulting in an increased expression of GLUT 4.
Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Ginsenosídeos/farmacologia , beta-Endorfina/efeitos dos fármacos , Animais , Diabetes Mellitus Experimental/metabolismo , Ginsenosídeos/uso terapêutico , Transportador de Glucose Tipo 4/biossíntese , Masculino , Camundongos , Panax , Fitoterapia , Ratos , Ratos Wistar , Receptores Opioides mu/metabolismo , EstreptozocinaRESUMO
We investigate the mechanism(s) of plasma glucose lowering action of puerarin in streptozotocin-induced diabetic rats (STZ-diabetic rats). Puerarin at the effective dosage to lower higher plasma glucose increased plasma beta-endorphin-like immunoreactivity (BER) in STZ-diabetic rats. Both effects of puerarin were abolished by the pretreatment with prazosin. Also, puerarin enhanced BER release from isolated rat adrenal medulla in a concentration-dependent manner that can be abolished by prazosin. Moreover, bilateral adrenalectomy in STZ-diabetic rats eliminated the actions of puerarin including the plasma glucose lowering effect and plasma BER elevating effect. In addition, naloxone and naloxonazine inhibited the plasma glucose lowering action of puerarin. Unlike in wild-type diabetic mice, puerarin failed to lower the plasma glucose in opioid micro-receptor knockout diabetic mice. In conclusion, our results suggest that puerarin may activate alpha (1)-adrenoceptors on the adrenal gland to enhance the secretion of beta-endorphin to result in a decrease of plasma glucose in STZ-diabetic rats.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Isoflavonas/farmacologia , Fitoterapia , Pueraria , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/induzido quimicamente , Relação Dose-Resposta a Droga , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Isoflavonas/administração & dosagem , Isoflavonas/uso terapêutico , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Estreptozocina , beta-Endorfina/efeitos dos fármacosRESUMO
Clients report more pain at some times of day than at others due, in part, to the temporal variation of the body's inhibitory pain response. The analgesic effectiveness of morphine varies with the time of day, perhaps due to the inhibiting or enhancing effects of the drug on plasma beta-endorphin (BE). This experiment was designed to examine the timed effects of morphine on the pain-induced BE response. Six groups of treatment mice (injected with morphine sulfate) and 6 groups of control mice (injected with saline) were exposed to an acute pain stimulus at 4-h intervals, and blood was collected. Plasma BE was analyzed using radioimmunoassay. Control mice showed a robust circadian BE-response rhythm with a peak at 0000 and a nadir at 1200, whereas the BE response of mice that received morphine was arrhythmic. Animals that received morphine tolerated the noxious stimulus longer, but the analgesia varied with time of day. These results indicate that morphine abolishes the rhythmic BE response to pain and does not inhibit pain equally at all times of day. Morphine doses should be titrated to maximize the endogenous pain control system while achieving analgesia with decreased dosages.
Assuntos
Analgésicos Opioides/uso terapêutico , Transtornos Cronobiológicos/tratamento farmacológico , Transtornos Cronobiológicos/metabolismo , Modelos Animais de Doenças , Morfina/uso terapêutico , Dor/tratamento farmacológico , Dor/metabolismo , beta-Endorfina/sangue , beta-Endorfina/efeitos dos fármacos , Doença Aguda , Analgésicos Opioides/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Cronoterapia , Avaliação Pré-Clínica de Medicamentos , Monitoramento de Medicamentos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos DBA , Morfina/farmacologia , Medição da Dor , Limiar da Dor/efeitos dos fármacos , Limiar da Dor/fisiologia , Radioimunoensaio , Tempo de Reação , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: Little is known about the influence of acupuncture treatment on the phagocytic immune system. This trial was performed to examine whether multiple acupuncture treatment affects the respiratory burst (RB) of neutrophils, a recognised measure of their cytotoxicity. DESIGN: Placebo-controlled single-blinded study. INTERVENTIONS: Eleven volunteers were treated bilaterally with standard needles (real) at acupoint LI11, 11 volunteers with placebo needles (placebo) at the same point. Treatments were performed for 30 min each twice a week for 4 weeks, eight times in all. The standard needles were manipulated until needle sensation (DEQI) developed. Before the treatment course (baseline), 48 h after the fourth (follow-up 1) and 48 h after the last treatment (follow-up 2) blood samples were drawn. MAIN OUTCOME MEASURES: RB and plasma beta-endorphin at each time point. RESULTS: In the real group there was a highly significant increase in the RB at follow-ups 1 (P=0.004) and 2 (P=0.007). Beta-endorphin levels decreased, but not significantly. In the placebo group there was a significant increase in the RB at follow-up 2 (P=0.048). In addition, at follow-up 2 a significant drop in beta-endorphin levels was observed (P=0.015). CONCLUSIONS: The RB of neutrophils is significantly activated by a course of several acupuncture treatments. In addition, psychological effects and a placebo that was not totally inert may contribute to the findings in the placebo group which may be mediated by the opiate endorphin system.
Assuntos
Terapia por Acupuntura , N-Formilmetionina Leucil-Fenilalanina/análogos & derivados , Neutrófilos/fisiologia , Explosão Respiratória/fisiologia , beta-Endorfina/sangue , Adulto , Escherichia coli/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Neutrófilos/efeitos dos fármacos , Explosão Respiratória/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , beta-Endorfina/efeitos dos fármacosRESUMO
Studies show that estrogens can influence alcohol consumption; however, findings are variable and an etiology remains unknown. Furthermore, estrogen administration can alter several neurotransmitter systems implicated in alcohol consumption, including the beta-endorphin (beta-EP) system. The present studies investigate (a) whether estradiol valerate (EV) alters voluntary alcohol consumption in Wistar and Lewis rats, (b) if an effect of EV on drinking is associated with changes in hypothalamic or pituitary beta-EP content, and (c) whether differences in alcohol drinking between treatment and rat groups are related to locomotor or defensive behavior/anxiety scores. Of 30 Wistar and 30 Lewis rats used in this study, half were injected with 2 mg EV in 0.2 ml sesame oil, while the remainder were injected with the vehicle only. After 8 weeks, all animals were tested in the open field and elevated plus maze. A week later, 4-6 animals in each group were sacrificed. The remaining animals were tested for voluntary alcohol drinking for 24 days prior to being sacrificed on the last day. Radioimmunoassay was used to estimate hypothalamic and pituitary beta-EP content. Wistar and Lewis rats injected with EV showed an increase in alcohol drinking, but their behavior scores and beta-EP levels remained unaltered. This result suggests that any EV effect on drinking is unrelated to changes in beta-EP or behavioral performance. Furthermore, Wistar rats show higher alcohol drinking, locomotor and defensive behavior scores, and hypothalamic beta-EP than Lewis rats. Higher alcohol drinking by Wistar rats might be due to higher behavioral scores or endogenous opioid activity/sensitivity.
Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Comportamento de Ingestão de Líquido/fisiologia , Estradiol/análogos & derivados , Estradiol/fisiologia , Etanol/metabolismo , beta-Endorfina/metabolismo , Análise de Variância , Animais , Ansiedade/induzido quimicamente , Ansiedade/metabolismo , Comportamento de Ingestão de Líquido/efeitos dos fármacos , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Feminino , Hipotálamo/química , Hipotálamo/metabolismo , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Hipófise/química , Hipófise/metabolismo , Ratos , Ratos Endogâmicos Lew/metabolismo , Ratos Wistar/metabolismo , Especificidade da Espécie , beta-Endorfina/análise , beta-Endorfina/efeitos dos fármacosRESUMO
Beta-endorphin is an endogenous opioid peptide implicated in reward processes, but the brain sites directly involved in its putative role in reward have not been identified. Here we used in vivo microdialysis in rats to study the effect of a potent reinforcer, lateral hypothalamus self-stimulation (LHSS), on the extracellular levels of beta-endorphin in the nucleus accumbens (NAS). The NAS is involved in the reinforcing effects of natural and artificial rewards, has high density of opioid receptors and is innervated by arcuate nucleus beta-endorphin neurons. LHSS had no effect on extracellular levels of beta-endorphin in the NAS. Surprisingly, extinction of the self-stimulation behaviour induced a rapid increase in NAS beta-endorphin levels. In a subsequent experiment in rats previously trained to self-administer heroin for 10 days, beta-endorphin levels also were increased during a test for extinction of the heroin-reinforced behaviour. Finally, the increase in extracellular beta-endorphin levels in the NAS was also observed during exposure to an aversive stimulus, intermittent footshock (20 min). These results indicate a possible role for increased levels of NAS beta-endorphin in the organism's adaptive response to stress and frustration.
Assuntos
Núcleo Accumbens/metabolismo , beta-Endorfina/metabolismo , Adaptação Fisiológica/fisiologia , Animais , Estimulação Elétrica , Extinção Psicológica/fisiologia , Espaço Extracelular/química , Heroína/administração & dosagem , Heroína/farmacologia , Hipotálamo/fisiologia , Masculino , Microdiálise , Entorpecentes/administração & dosagem , Entorpecentes/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Ratos , Recompensa , Autoadministração , Autoestimulação , beta-Endorfina/análise , beta-Endorfina/efeitos dos fármacosRESUMO
OBJECTIVES: Several natural or synthetic estrogenic molecules are commonly used in oral hormone replacement therapy for the relief of menopausal complaints and for the primary prevention of cardiovascular disease and osteoporosis. Little information is available concerning the comparative efficacy of different compounds on neuroendocrine function. The opioid peptide beta-endorphin (beta-EP), and the neurosteroid allopregnanolone are considered markers of neuroendocrine function and their synthesis and action is regulated by gonadal steroids. The present study aimed to investigate the effects of a 2-week oral treatment with estradiol valerate (EV), estrone sulphate (ES), or conjugated equine estrogen (CEE) on central and peripheral beta-EP and allopregnanolone levels in ovariectomized (OVX) female rats. METHODS: Twelve groups of Wistar OVX rats received oral EV (0.05, 0.1, 0.5 and 1 mg/Kg/day) or ES (0.1, 0.5, 1 and 2 mg/Kg/day), or CEE (0.1, 0.5, 1 and 2 mg/Kg/day) for 14 days. One group of fertile and one group of OVX rats were used as controls. beta-EP content was assessed in hypothalamus, hippocampus, anterior and neurointermediate pituitary, and plasma, while allopregnanolone content was assessed in hypothalamus, hippocampus, anterior pituitary, adrenals and serum. RESULTS: Ovariectomy induced a significant decrease in beta-EP and allopregnanolone content in hypothalamus, hippocampus, pituitary, and serum, while it increased allopregnanolone content in the adrenals. In OVX rats, the administration of each molecule reversed the ovariectomy-induced beta-EP and allopregnanolone changes in a dose-dependent fashion, therefore completely restoring their concentration. At higher doses, the estrogenic compounds induced significantly higher levels of allopregnanolone and beta-EP than in fertile rats. CEE induced higher allopregnanolone levels in hypothalamus, anterior pituitary and serum than the other estrogenic molecules, and in the hippocampus with respect to EV alone. CEE produced higher beta-EP levels in the hippocampus and hypothalamus with respect to EV and ES. CONCLUSION: In the examined tissue and serum estrogens restore the ovariectomy induced changes in allopregnanolone and beta-EP content in a dose-dependent manner; the magnitude of these effects is not uniform and it is related to the different tissues and the employed compounds.
Assuntos
Estradiol/análogos & derivados , Estradiol/farmacologia , Estrogênios Conjugados (USP)/farmacologia , Estrona/análogos & derivados , Estrona/farmacologia , Pregnanolona/metabolismo , beta-Endorfina/efeitos dos fármacos , Administração Oral , Animais , Relação Dose-Resposta a Droga , Estradiol/administração & dosagem , Terapia de Reposição de Estrogênios , Estrogênios Conjugados (USP)/administração & dosagem , Estrona/administração & dosagem , Feminino , Hipocampo/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Ovariectomia , Hipófise/efeitos dos fármacos , Pregnanolona/sangue , Ratos , Ratos Wistar , Útero/efeitos dos fármacos , beta-Endorfina/sangue , beta-Endorfina/metabolismoRESUMO
It is known that pain suppression in animals is induced by certain environmental stimulus. However, little is known about the effects of gravitational alteration on the nociceptive responses in rats. A recent study indicated that Fos protein expression was strongly induced in the vestibular-related brainstem regions of rats that were exposed to 2 G hypergravity (Gustave Dit Duflo et al., 2000). A number of studies indicate that Fos expression is induced in the brain by various kinds of stress. We showed that either long-term exposure or short-term exposure to 2 G hypergravity elevated the nociceptive threshold in the rat skin surfaces, in concomitant with Fos induction in the hypothalamus including the arcuate nucleus and paraventricular nucleus (Kumei et al., 2000). We have examined the possible involvement of beta-endorphin, an endogenous opioid, in the hypergravity-induced analgesic effects on rats and its counteraction by naloxone, an opioid receptor antagonist.
Assuntos
Hipergravidade , Nociceptores/fisiologia , Limiar da Dor/fisiologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , beta-Endorfina/metabolismo , Animais , Hipotálamo/metabolismo , Masculino , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Limiar da Dor/efeitos dos fármacos , Ratos , Ratos Wistar , Pele , beta-Endorfina/efeitos dos fármacosRESUMO
Cocoa and chocolate contain the tetrahydroisoquinoline alkaloid salsolinol up to a concentration of 25 microg/g. Salsolinol is a dopaminergic active compound which binds to the D(2) receptor family, especially to the D(3) receptor with a K(i) of 0.48+/-0.021 micromol/l. It inhibits the formation of cyclic AMP and the release of beta-endorphin and ACTH in a pituitary cell system. Taking the detected concentration and the pharmacological properties into account, salsolinol seems to be one of the main psychoactive compounds present in cocoa and chocolate and might be included in chocolate addiction.
Assuntos
Cacau/química , Isoquinolinas/farmacologia , Receptores Dopaminérgicos/efeitos dos fármacos , Células Tumorais Cultivadas/efeitos dos fármacos , Hormônio Adrenocorticotrópico/metabolismo , Animais , Cacau/fisiologia , AMP Cíclico/metabolismo , Análise de Alimentos , Cromatografia Gasosa-Espectrometria de Massas , Isoquinolinas/análise , Isoquinolinas/metabolismo , Camundongos , Receptores Dopaminérgicos/metabolismo , Estereoisomerismo , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Células Tumorais Cultivadas/metabolismo , beta-Endorfina/efeitos dos fármacos , beta-Endorfina/metabolismoRESUMO
OBJECTIVES: A progressive decline of plasma dehydroepiandrosterone (DHEA) levels occurs in women during aging related to the reduction of adrenocortical secretion. A specific action of DHEA on the central nervous system (CNS) is suggested by the improvement of psychological and physical well-being in postmenopausal women after DHEA supplementation. The aim of the present study was to investigate the neuroendocrine effects of short-term DHEA supplementation in postmenopausal women, evaluating changes of plasma beta-endorphin (beta-EP) and growth hormone (GH) before and after oral DHEA (100 mg/day) for 7 days in postmenopausal women (n = 6). METHODS: Before and after 7 days of DHEA supplementation, postmenopausal women underwent a neuroendocrine test with clonidine, an alpha 2 presinaptic agonist for adrenergic system (1.25 mg i.v.). Basal plasma DHEA, androstenedione (A), testosterone (T), estrone (E1) and estradiol (E2) levels were evaluated before and after treatment, while plasma beta-EP and GH levels were measured before and 15, 30, 45, 60 and 90 min after clonidine injection. RESULTS: Basal plasma beta-EP and GH levels did not show a significant difference before and after short-term DHEA administration, while circulating A, T, E1 and E2 significantly increased after treatment. The clonidine test induced a significant increase of plasma beta-EP levels in women after receiving DHEA supplementation but not before; conversely, plasma GM levels increased both before and after treatment. CONCLUSIONS: The present study indicates that short-term DHEA supplementation in postmenopausal women is able to restore the impaired response of pituitary beta-EP to clonidine, an alpha 2 presinaptic agonist. According to these data it is possible to hypothesize that DHEA could play a role in the psychological and physical well-being of postmenopausal women acting via a restoration of neuroendocrine control of antero-pituitary beta-EP secretion.
Assuntos
Desidroepiandrosterona/farmacologia , Hormônio do Crescimento Humano/efeitos dos fármacos , Sistemas Neurossecretores/efeitos dos fármacos , Pós-Menopausa/efeitos dos fármacos , beta-Endorfina/efeitos dos fármacos , Administração Oral , Androstenodiona/sangue , Androstenodiona/metabolismo , Clonidina , Desidroepiandrosterona/administração & dosagem , Desidroepiandrosterona/sangue , Desidroepiandrosterona/metabolismo , Estrona/sangue , Estrona/metabolismo , Feminino , Hormônio do Crescimento Humano/sangue , Hormônio do Crescimento Humano/metabolismo , Humanos , Pessoa de Meia-Idade , Sistemas Neurossecretores/metabolismo , Pós-Menopausa/sangue , Simpatolíticos , Testosterona/sangue , Testosterona/metabolismo , beta-Endorfina/sangue , beta-Endorfina/metabolismoRESUMO
The effect of trichosanthin on levels of the neuropeptides beta-endorphin (beta-EP) and methionine enkephalin (met-EK) in the mouse brain and pituitary was investigated. Mature male ICR mice were divided into two groups. One group received intravenous injections of physiological saline and served as the control. Another group received daily intravenous injections of trichosanthin (0.2 mg/25g/injection) for three consecutive days. The animals were sacrificed four hours after the last injection. Their brains were dissected into three regions: A (thalamus and hypothalamus), B (cerebral cortex) and C (cerebellum and brainstem) and their pituitaries were collected. The samples were then extracted and assayed for beta-EP and met-EK by specific radioimmunoassays. It was found that there were no statistically significant changes in the levels of the two neuropeptides in the pituitary and the brain regions except for the level of beta-EP in brain region A.
Assuntos
Encéfalo/metabolismo , Encefalina Metionina/biossíntese , Hipófise/metabolismo , Tricosantina/farmacologia , beta-Endorfina/biossíntese , Animais , Fármacos Anti-HIV/farmacologia , Encéfalo/anatomia & histologia , Encéfalo/efeitos dos fármacos , Encefalina Metionina/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Injeções Intravenosas , Masculino , Camundongos , Camundongos Endogâmicos ICR , Hipófise/efeitos dos fármacos , Ribossomos/metabolismo , Tálamo/efeitos dos fármacos , Tálamo/metabolismo , beta-Endorfina/efeitos dos fármacosRESUMO
Recent pharmacological and morphological studies have raised the likelihood of a regulatory link between the neuropeptide Y (NPY) and beta-endorphin (beta-END) networks in the hypothalamus. To evaluate this link we have examined the effects of NPY administration on the in vivo release of beta-END by push-pull perfusion of the basal hypothalamus. Results showed that centrally injected NPY stimulated the in vivo release of beta-END. This effect was evident only in the absence of testicular steroids since NPY failed to alter beta-END release in intact rats. These data suggest that the well-documented effects of NPY such as inhibition of pituitary gonadotropin release in gonadectomized rats and stimulation of feeding may be mediated, in part, by stimulation of beta-END.
Assuntos
Gônadas/fisiologia , Hipotálamo/metabolismo , Hormônio Luteinizante/fisiologia , Neuropeptídeo Y/farmacologia , beta-Endorfina/efeitos dos fármacos , Animais , Masculino , Microinjeções , Orquiectomia , Radioimunoensaio , Ratos , Ratos Endogâmicos , Esteroides/fisiologia , beta-Endorfina/metabolismoRESUMO
1. Haloperidol increased the Met-enk level in the striatum at all age groups. However, the Met-enk level was decreased in AL of young and middle-aged rats by the drug. 2. Haloperidol elevated the beta-end level in AL and CCK level in NIL in young rats only. 3. The SP content in NIL was decreased by haloperidol in all age groups. 4. With regard to the effect of aging, Met-enk level in AL of middle-aged rats was higher than that in young rats. The beta-end level in AL also increased in old rats. 5. Aging modified the haloperidol effect on beta-end level in AL and CCK level in NIL as the effect was only observed in young rats. 6. In addition, aging caused a blunted response of Met-enk level to haloperidol in the striatum but an increased response of SP content to haloperidol in the NIL.
Assuntos
Colecistocinina/efeitos dos fármacos , Corpo Estriado/efeitos dos fármacos , Encefalina Metionina/efeitos dos fármacos , Haloperidol/farmacologia , Hipotálamo/efeitos dos fármacos , Hipófise/efeitos dos fármacos , Substância P/efeitos dos fármacos , beta-Endorfina/efeitos dos fármacos , Envelhecimento/metabolismo , Animais , Hipotálamo/metabolismo , Masculino , Hipófise/metabolismo , Radioimunoensaio , Ratos , Ratos Sprague-DawleyRESUMO
The aim of this study was to investigate time-related changes in substance P (SP) beta-endorphin (BE), and corticosteron (CORT) levels induced by DSIP administration in rats subjected to emotional stress. Experiments were carried out in male Wistar and August rats with different resistance to emotional stress. At night rats were tied by their tails to the backside of the special cages. These stress-inducing procedure was repeated for 12 hours daily in the course of 5 days. SP and BE immunoreactivity in the hypothalamus and plasma and blood CORT level were determined radioimmunologically. Six groups of animals were formed: 1. control animals; 2. stressed animals; 3. rats which received DSIP in a dose of 60 nmol/kg one hour before decapitation; 3. rats to which DSIP was injected 24 hours before decapitation; 5. stressed rats to which DSIP was injected one hour before decapitation during the 5th exposure to stress; 6. stressed rats to which DSIP was injected 12 hours before the 5th exposure to stress, i.e. 24 hours before decapitation. Our experiments showed that DSIP administration induced marked changes in SP, BE, and CORT levels in the hypothalamus and blood plasma. This suggests that long-term stress-coping effects of DSIP in underlied by considerable changes in the content of other oligopeptides and hormones. Evidently, DSIP triggers these processes inducing a cascade of interrelated molecular reactions which are different in Wistar and August rats. It seems likely that DSIP administration stimulates the mechanisms of resistance in August rats to a lesser extent than in Wistar rats.
Assuntos
Corticosterona/metabolismo , Peptídeo Indutor do Sono Delta/farmacologia , Hipotálamo/efeitos dos fármacos , Estresse Psicológico/metabolismo , Substância P/efeitos dos fármacos , beta-Endorfina/efeitos dos fármacos , Análise de Variância , Animais , Química Encefálica/efeitos dos fármacos , Química Encefálica/fisiologia , Corticosterona/análise , Hipotálamo/química , Hipotálamo/metabolismo , Masculino , Ratos , Ratos Endogâmicos , Ratos Wistar , Substância P/análise , Substância P/metabolismo , Fatores de Tempo , beta-Endorfina/análise , beta-Endorfina/metabolismoRESUMO
Chronic alcoholic intoxication is followed by a fall in 3H-(D-ala-2,D-leu-5)-enkephalin affinity of mu-opioid receptors with their unchanged concentrations in the rat brain cortex, by reductions in the tissue and plasma levels of beta-endorphine and met-enkephalin. A daily administration of reaferon in a dose of 10,000 IU during two fortnights completely restored both the binding affinity of the receptors and the concentrations of the peptides tested: those of beta-endorphine in the adenohypophysis and plasma and those of metenkephalin in the adrenals and plasma.
Assuntos
Dissuasores de Álcool/uso terapêutico , Alcoolismo/tratamento farmacológico , Interferon Tipo I/uso terapêutico , Receptores Opioides/efeitos dos fármacos , Dissuasores de Álcool/farmacologia , Alcoolismo/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Química Encefálica/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Encefalina Metionina/efeitos dos fármacos , Encefalina Metionina/metabolismo , Interferon Tipo I/farmacologia , Interferon alfa-2 , Interferon-alfa , Ligantes , Masculino , Ligação Proteica/efeitos dos fármacos , Ensaio Radioligante , Ratos , Receptores Opioides/análise , Receptores Opioides/metabolismo , Proteínas Recombinantes , beta-Endorfina/efeitos dos fármacos , beta-Endorfina/metabolismoRESUMO
The present study was conducted to evaluate and compare effects of the benzodiazepine agonist diazepam, antagonist flumazenil and inverse agonist RO 15-4513 on ethanol-induced changes in beta-endorphin (beta-EN) levels in specific rat brain regions. Male Sprague-Dawley rats (150-200 g) adapted to a 12-hour light:12-hour dark illumination cycle were used in this study. Ethanol (3 g/kg as 22.5% solution in saline), flumazenil (10 mg/kg), RO 15-4513 (10 mg/kg), diazepam (2 mg/kg) or a combination of ethanol (3 g/kg) and flumazenil (10 mg/kg), RO 15-4513 (10 mg/kg) or diazepam (2 mg/kg) were administered intraperitoneally to rats at 7.00 h. Control animals were injected with saline. Animals were sacrificed by decapitation 1 h after injection; the brains were immediately removed; the cortex, hippocampus and hypothalamus were dissected and their beta-EN levels measured by radioimmunoassay. Ethanol administration significantly increased beta-EN levels in the hippocampus and hypothalamus but had no effect on beta-EN levels in the cortex. Similar increases in beta-EN levels in the hippocampus and hypothalamus also occurred following either flumazenil or diazepam. On the other hand, RO 15-4513 significantly increased beta-EN levels in the cortex and hypothalamus. When flumazenil was concurrently administered with ethanol, it completely reversed the ethanol effects in the hippocampus but failed to do so in the hypothalamus. Concurrent administration of RO 15-4513 with ethanol also reversed the ethanol-induced rise of beta-EN in the hypothalamus. However, concurrent administration of diazepam and ethanol did not block the increase in beta-EN levels.(ABSTRACT TRUNCATED AT 250 WORDS)