RESUMEN
The twitch procedure in horses attenuates the increase in the heart rate evoked by pain-inducing stimuli and the reaction of the animals to such stimuli. Endorphin systems are probably involved in the effectiveness of the twitch, since its action is blocked by naloxone and its application increases plasma concentrations of immunoreactive beta-endorphin. The mode of action of the twitch cannot be explained by the generally accepted theory of divertive pain and may resemble that of classical acupuncture.
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Caballos/fisiología , Dolor/fisiología , Terapia por Acupuntura , Animales , Endorfinas/sangre , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Naloxona/farmacología , Estimulación Física , betaendorfinaRESUMEN
We have investigated transmitter release from small and large dense-core vesicles in nerve terminals isolated from guinea pig hippocampus. Small vesicles are found in clusters near the active zone, and large dense-core vesicles are located at ectopic sites. The abilities of Ca2+ channel activation and uniform elevation of Ca2+ concentration (with ionophores) to evoke secretion of representative amino acids, catecholamines, and neuropeptides were compared. For a given increase in Ca2+ concentration, ionophore was less effective than Ca2+ channel activation in releasing amino acids, but not in releasing cholecystokinin-8. Titration of the average Ca2+ concentration showed that the Ca2+ affinity for cholecystokinin-8 secretion was higher than that for amino acids. Catecholamine release showed intermediate behavior. It is concluded that neuropeptide release is triggered by small elevations in the Ca2+ concentration in the bulk cytoplasm, whereas secretion of amino acids requires higher elevations, as produced in the vicinity of Ca2+ channels.
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Aminoácidos/metabolismo , Catecolaminas/metabolismo , Terminaciones Nerviosas/metabolismo , Neuropéptidos/metabolismo , Animales , Calcio/metabolismo , Exocitosis/fisiología , Cobayas , Potenciales de la Membrana , Norepinefrina/metabolismo , Sincalida/metabolismo , Sinaptosomas/ultraestructuraRESUMEN
BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with altered hypothalamic-pituitary-adrenal (HPA) axis functioning. Arginine vasopressin (AVP), in conjunction with corticotrophin releasing hormone, has shown to be an important modulator of the HPA axis. In order to evaluate the effect of trauma and PTSD on central AVP secretion we assessed plasma AVP levels in equally trauma exposed veterans with and without PTSD and a non-traumatized healthy control group. METHODS: Assessment of plasma AVP in 29 male veterans with PTSD, 29 traumatized veterans without PTSD, matched for age, gender, year and region of deployment (trauma controls), and 26 age matched healthy controls. RESULTS: Plasma AVP levels were higher in PTSD patients compared to both healthy controls (p = 0.004) and trauma controls (p < 0.001). In PTSD patients without a comorbid MDD a significant correlation was observed between plasma AVP levels and symptoms of avoidance measured with the Clinician Administered PTSD Scale (CAPS). CONCLUSION: Elevated plasma AVP levels are specifically related to PTSD and not to exposure to traumatic stress during deployment. Our results indicate that AVP may play a role as an anxiogenic factor, but they do not support a role for AVP in the altered response to dexamethasone in PTSD.
Asunto(s)
Arginina Vasopresina/sangre , Trastornos por Estrés Postraumático/sangre , Veteranos/psicología , Adulto , Hormona Liberadora de Corticotropina/metabolismo , Humanos , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipotálamo-Hipofisario/fisiopatología , Masculino , Sistema Hipófiso-Suprarrenal/metabolismo , Sistema Hipófiso-Suprarrenal/fisiopatología , Escalas de Valoración Psiquiátrica , Psicometría , Trastornos por Estrés Postraumático/diagnóstico , Trastornos por Estrés Postraumático/fisiopatologíaRESUMEN
UNLABELLED: Although schizophrenia usually sets on after puberty, deviations of normal development exist in pre-schizophrenic children. To investigate the presence of early developmental abnormalities in a valid animal model for schizophrenia, we delineated line-specific developmental differences between apomorphine-susceptible rats (APO-SUS), which share many features with schizophrenic patients, and their counterpart, apomorphine-unsusceptible rats (APO-UNSUS). A battery of somatic developmental markers was assessed in naive animals on postnatal day (PND) 4 and in animals from PND 0 to PND 60. Three comparisons were made: naive APO-SUS and naive APO-UNSUS rats on PND 4; naive and handled APO-SUS and APO-UNSUS rats on PND 4; handled APO-SUS rats and handled APO-UNSUS rats across the initial 60 PND's. Naive APO-SUS rats developed much slower than naive APO-UNSUS rats as far as it concerns digit-separation, anogenital-distance, rooting-reflex, and body-displacement on PND 4, thereby underlining the validity of the APO-SUS rats as model for aspects of schizophrenia. Handling on PND 0-3 retarded the development of both types of rat, implying that early life events have long-lasting effects on pure-somatic markers. Finally, handling from PND 0 to PND 60 had a more pronounced retardation effect in APO-UNSUS rats than in APO-SUS rats. It is suggested that the APO-SUS rats are not affected as much as the APO-UNSUS rats, because they are already overwhelmed by other subliminal stimuli that have no effect on APO-UNSUS rats. IN CONCLUSION: (1) the APO-SUS rat, which is a valid model for schizophrenia, has a retarded development just as pre-schizophrenic children have; (2) early postnatal manipulations have immediate and long-lasting effects on the rodents' morphology; and (3) subchronic, early postnatal handling has a greater effect in APO-UNSUS rats than in APO-SUS rats. The impact of these data for APO-SUS rats as a model for schizophrenia is discussed.
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Animales Recién Nacidos/crecimiento & desarrollo , Apomorfina/farmacología , Agonistas de Dopamina/farmacología , Manejo Psicológico , Esquizofrenia/fisiopatología , Estrés Psicológico/fisiopatología , Factores de Edad , Análisis de Varianza , Animales , Biomarcadores , Modelos Animales de Enfermedad , Femenino , Genotipo , Masculino , Fenotipo , Ratas , Ratas Endogámicas , Especificidad de la Especie , Conducta Estereotipada/efectos de los fármacosRESUMEN
A single session of foot shock stress produces stable and long lasting sensitization of behavioral, hormonal and intestinal motility responses to novel stressful stimuli in laboratory rats. This is reflected in increased expression of the activity marker protein Fos in brain areas involved, following an external stressor. We present data from awake, freely moving rats in which a silicone balloon was surgically implanted in the duodenum. Firstly, cardiovascular reflexes to distentions were studied using telemetry with surgically implanted transmitters, 2 weeks after a single, 15-min session of foot shocks. The distentions caused characteristic, bi-phasic responses in both mean arterial blood pressure and heart rate that were not different between preshocked and control animals. Secondly, the numbers of Fos immunopositive cells were quantified in selected brain areas, 1 h after repeated distention of the duodenum. We found an increase in distention-induced Fos in preshocked rats in the nucleus tractus solitarius and a weaker effect in the central nucleus of the amygdala. This could be a first indication that altered visceral afferent processing in previously stressed rats, found earlier for the colon, may be a general and not an organ-specific phenomenon.
Asunto(s)
Tronco Encefálico/fisiopatología , Duodeno/inervación , Duodeno/fisiología , Potenciales Evocados Somatosensoriales , Dolor/fisiopatología , Estimulación Física/efectos adversos , Proteínas Proto-Oncogénicas c-fos/metabolismo , Estrés Psicológico/fisiopatología , Adaptación Fisiológica , Animales , Presión Sanguínea , Frecuencia Cardíaca , Masculino , Dolor/etiología , Estimulación Física/métodos , Ratas , Ratas Wistar , Estrés Psicológico/etiologíaRESUMEN
The role of endogenous opioid mechanisms in the pituitary-adrenocortical response to acute stress was investigated in a longitudinal study in cyclic female pigs before and after exposure to chronic stress (long term tethered housing). Challenge of loose-housed pigs with acute nose-sling stress for 15 min induced an activation of the hypothalamic-pituitary-adrenocortical axis, evidenced by a transient increase in plasma ACTH (peak height above basal, 98 +/- 12 pg/ml; mean +/- SEM) and cortisol (54 +/- 3 ng/ml) concentrations. Pretreatment with the opioid receptor antagonist naloxone (0.5 mg/kg BW, iv bolus) increased the challenge-induced ACTH and cortisol responses to 244 +/- 36 pg/ml and 65 +/- 5 ng/ml, respectively. This indicates that during acute nose-sling stress, endogenous opioid systems are activated that inhibit the pituitary-adrenocortical response. After exposure of the pigs to chronic stress (10-11 weeks of tethered housing), the challenge-induced ACTH response was attenuated, whereas the cortisol response remained unchanged, suggesting an increased adrenocortical sensitivity to circulating ACTH. In addition, pretreatment with naloxone induced a greater increment in the ACTH and cortisol responses in tethered pigs than in loose-housed pigs. As no such changes were found in control animals housed loose during the entire experimental period, this indicates that the impact of opioid systems had increased due to chronic stress. The increased impact of opioid systems during chronic stress may prevent excessive hypothalamic-pituitary-adrenocortical responses to acute stressors and, thus, may be of adaptive value.
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Corteza Suprarrenal/fisiopatología , Péptidos Opioides/fisiología , Hipófisis/fisiopatología , Estrés Fisiológico/fisiopatología , Porcinos/fisiología , Hormona Adrenocorticotrópica/sangre , Animales , Femenino , Hidrocortisona/sangre , Cinética , Naloxona/farmacología , Restricción FísicaRESUMEN
In the present study we investigated how the suprachiasmatic nucleus (SCN) controls the E(2)-induced PRL surge in female rats. First, the role of vasopressin (VP), a SCN transmitter present in medial preoptic area (MPO) projections and rhythmically released by SCN neurons, as a circadian signal for the E(2)-induced PRL surge was investigated. Using a reverse microdialysis technique, VP was administered in the MPO during the PRL surge, resulting in a suppression of the surge. VP administration before the surge did not affect PRL secretion. Also, administration of a V1a receptor antagonist before the surge was ineffective. Second, lesions of the SCN were made that resulted in constant basal PRL levels, suggesting that with removal of the SCN a stimulatory factor for PRL secretion disappeared. Indeed, the PRL secretory response to blockade of pituitary dopamine receptors was significantly reduced in SCN-lesioned animals. These data suggest that the afternoon decrease of VP release in the MPO by SCN terminals enables the PRL surge to occur, and may thus be a circadian signal for the PRL surge. Simultaneously the SCN is involved in the regulation of the secretory capacity of the pituitary, possibly via specific PRL-releasing factors.
Asunto(s)
Estradiol/farmacología , Prolactina/metabolismo , Núcleo Supraquiasmático/fisiología , Animales , Ritmo Circadiano , Implantes de Medicamentos , Estradiol/administración & dosificación , Femenino , Microdiálisis , Ovariectomía , Área Preóptica/efectos de los fármacos , Área Preóptica/fisiología , Proestro , Ratas , Ratas Wistar , Núcleo Supraquiasmático/cirugía , Vasopresinas/metabolismo , Vasopresinas/farmacologíaRESUMEN
In small rodents, reproduction is critically dependent on the integrity of the circadian oscillator of the brain, the suprachiasmatic nucleus (SCN). Lesions of the SCN induce persistent estrus (anovulation) in intact female rats, whereas estrogen implantation in ovariectomized rats results in daily LH surges, which disappear after SCN lesions. Vasoactive intestinal polypeptide (VIP), a peptide synthesized in cell bodies of the SCN, has been implicated in the regulation of LH release. Recently, we have provided immunocytochemical evidence for a VIP-containing neuronal projection from the SCN to the GnRH system. This suggests that VIP from the SCN may modulate LH release via a direct influence on GnRH neurons. To investigate the involvement of VIP input on GnRH neurons and SCN neurons in the generation of a LH surge, we used immunoreactive c-fos as a marker for cell activation in ovariectomized mature rats and immature rats treated with steroids. VIP-containing fibers were observed in apposition to a substantial portion of the GnRH neurons containing c-fos. Expression of c-fos was more frequently observed in VIP-innervated GnRH neurons than in GnRH neurons in general. This difference in activation was most pronounced during the onset of the LH surge. In SCN neurons, steroid treatment did not induce c-fos immunoreactivity before or during the LH surge. The present results indicate that VIP-containing fibers, possibly originating in the SCN, are involved in the initiation of the LH surge. In view of the reported inhibitory effects of VIP on LH release, it is suggested that the role of VIP input in this respect is permissive.
Asunto(s)
Hormona Liberadora de Gonadotropina/análisis , Hormona Luteinizante/metabolismo , Neuronas/química , Proteínas Proto-Oncogénicas c-fos/análisis , Péptido Intestinal Vasoactivo/análisis , Animales , Ritmo Circadiano , Estrógenos/farmacología , Femenino , Inmunohistoquímica , Masculino , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Ovariectomía , Progesterona/farmacología , Proteínas Proto-Oncogénicas c-fos/biosíntesis , Ratas , Ratas Wistar , Núcleo Supraquiasmático/química , Núcleo Supraquiasmático/fisiología , Núcleo Supraquiasmático/cirugíaRESUMEN
A number of recent studies suggest that cells of the immune system, e.g. peripheral blood mononuclear cells (PBMC), can synthesize and process POMC and secrete POMC-derived peptides, such as ACTH and endorphins, upon immune and hormonal challenges. From this, it has been proposed that POMC-derived peptides originating from lymphoid cells can function as hormones, for instance in a lymphoid-adrenal axis. In view of the important physiological implications of this proposal, the present study was designed to investigate the expression of the POMC gene in human PBMC and the production by these cells of alpha-, beta-, and gamma-endorphins (alpha E, beta E, and gamma E) peptides that are established end products of the posttranslational processing of POMC. PBMC of individual donors were used uncultured (fresh cells) or cultured for 24 and 48 h in the presence and absence of Concanavalin-A (Con-A), bacterial lipopolysaccharide, phytohemagglutinin, or CRH, and vasopressin, conditions that reportedly stimulate POMC activity in those cells, to investigate the presence of POMC transcripts by analysis of total RNA with Northern blotting and the reverse transcriptase polymerase chain reaction (RT-PCR). Large scale preparations containing over 10(9) cells (fresh, cultured with and without Con-A) originating from several donors were examined for the presence of POMC transcripts by analysis of poly(A)+ RNA on Northern blots and for the presence of alpha E, beta E, and gamma E by gel filtration over Sephadex G-75 and reverse phase HPLC, followed by assay of the fractions in four endorphin RIA systems with different specificities. On the Northern blots of total RNA, no POMC transcripts were detectable. In poly(A)+ RNA preparations, no full-length POMC mRNA was found, and it was estimated that the concentration of POMC mRNA, if present, was below approximately 0.005 transcript/cell in Con-A-stimulated cells and still lower in unstimulated cells. In accord with literature data, an 800- to 900-nucleotide POMC transcript was detected in cultured PBMC, and the levels of this transcript were stimulated by Con-A. In all samples analyzed with RT-PCR, a transcript spanning most of exons 2 and 3 was detectable only on Southern blots of the RT-PCR product, but not on agarose gels stained with ethidium bromide. Chromatographic analysis of endorphin immunoreactivities in cell extracts revealed no qualitative differences between the immunoreactive profiles of fresh PBMC or PBMC cultured with or without Con-A.(ABSTRACT TRUNCATED AT 400 WORDS)
Asunto(s)
Leucocitos Mononucleares/metabolismo , Linfocitos/metabolismo , Proopiomelanocortina/genética , ARN Mensajero/sangre , betaendorfina/análisis , Secuencia de Bases , Northern Blotting , Southern Blotting , Catepsina D/metabolismo , Cromatografía en Gel , Cromatografía Líquida de Alta Presión , Sondas de ADN , Humanos , Datos de Secuencia Molecular , Fragmentos de Péptidos/análisis , Mapeo Peptídico , Reacción en Cadena de la PolimerasaRESUMEN
The effect of intracisternal pretreatment with opiate antagonists or antisera against various opioid peptides on the hypotension and bradycardia induced by cumulative intracisternal administration of clonidine (0.02-2.5 microgram) was studied in conscious Wistar-Kyoto rats and in spontaneously hypertensive rats. No effect of any pretreatment on basal values of blood pressure and heart rate was detected in either of these strains. In spontaneously hypertensive rats intracisternal pretreatment with naltrexone resulted in a dose-dependent inhibition of clonidine-induced hypotension and bradycardia. DL-naloxone also antagonized the hypotension but not influence the hypotensive and bradycardic response to clonidine. In Wistar-Kyoto rats naltrexone and the beta-endorphin antiserum B4 failed to affect the cardiovascular effects of clonidine. B4 and an antiserum against dynorphin(1-13) inhibited clonidine-induced hypotension in spontaneously hypertensive rats, whereas a [Met5]enkephalin antiserum had no effect. Use of antisera specifically recognizing the C-terminus of beta-, alpha-, and gamma-endorphin, respectively, revealed that only the beta-endorphin antiserum inhibited the fall in blood pressure in spontaneously hypertensive rats after cumulative administration of clonidine. None of the antisera used affected clonidine-induced bradycardia. These results indicate that activation of stereospecific opiate receptors in spontaneously hypertensive, but not in Wistar-Kyoto rats, plays a role in the central hypotensive effect of clonidine. beta-Endorphin(1-31) and dynorphin(1-13) might be the endogenous ligands for these receptors.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Encéfalo/efectos de los fármacos , Clonidina/farmacología , Endorfinas/fisiología , Hipertensión/fisiopatología , Animales , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Naltrexona/farmacología , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas , Ratas Endogámicas WKY , Receptores Opioides/efectos de los fármacos , Glutamato de Sodio/farmacologíaRESUMEN
BACKGROUND: Arousal-regulating mechanisms are important in explaining individual differences in antisocial behavior. METHODS: Alterations in salivary cortisol concentration and cardiovascular activity were studied in 21 boys with oppositional defiant disorder (ODD) and 31 normal controls (NC) during a 2-hour stressful procedure involving frustration and provocation. RESULTS: Baseline levels of heart rate (HR) were significantly lower in the ODD group, but their HR levels were higher during provocation and frustration. Cortisol levels in the ODD group were overall lower than those of the NC group, and the effect of stress seemed to be minimal and similar for both groups; however, individual differences were large. Since anxiety plays an important mediating role in cortisol response, subjects were divided into one of four groups based on the intensity of their externalizing behavior and anxiousness. Cortisol increase due to stress exposure was strongest in highly externalizing and highly anxious subjects; cortisol decrease was strongest in those subjects who were high in externalizing behavior and low in anxiousness. CONCLUSIONS: The results of the study support an important role for hypothalamic-pituitary-adrenal axis sympathetic autonomic functioning in persistent antisocial behavior in young boys.
Asunto(s)
Trastornos Reactivos del Niño/metabolismo , Trastornos Reactivos del Niño/fisiopatología , Hemodinámica/fisiología , Hidrocortisona/metabolismo , Saliva/metabolismo , Estrés Psicológico/metabolismo , Estrés Psicológico/fisiopatología , Agresión/fisiología , Ira/fisiología , Presión Sanguínea/fisiología , Niño , Trastornos Reactivos del Niño/psicología , Frecuencia Cardíaca/fisiología , Humanos , Pruebas de Inteligencia , Masculino , Escalas de Valoración Psiquiátrica , Estrés Psicológico/psicologíaRESUMEN
BACKGROUND: Previously, we found that mean plasma concentrations of arginine vasopressin (AVP), but not of oxytocin (OT), were higher in depressed patients than in healthy controls. Plasma AVP concentrations were positively correlated to clinically rated psychomotor retardation. To further explore this previously reported relation we studied psychomotor retardation by means of an activity monitor, which is a more fine-focused and more objective instrument to analyze motor retardation than a clinical rating scale. METHODS: Plasma AVP and OT concentrations, and day- and nighttime wrist activity were measured in 48 in- and outpatients with major depression and 30 healthy controls during a period of 5 consecutive days and nights. RESULTS: Principal components analysis revealed three components of motor activity: motor activity during wakefulness, motor activity during sleep, and the awake/sleep time ratio. In patients and controls an inverse relationship between plasma AVP concentrations and motor activity during wakefulness was found. Patients with elevated AVP plasma levels showed increased motor activity during sleep. CONCLUSIONS: These results suggest that high plasma AVP levels are related to the clinical picture of daytime psychomotor retardation and nighttime motor activity in major depression. Mean plasma OT concentrations were not related to measures of motor activity.
Asunto(s)
Arginina Vasopresina/sangre , Trastorno Depresivo/sangre , Trastorno Depresivo/psicología , Actividad Motora/fisiología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxitocina/sangre , Escalas de Valoración Psiquiátrica , Sueño/fisiología , Vigilia/fisiologíaRESUMEN
alpha-Endorphin and gamma-endorphin, two closely related peptides of the pro-opiomelanocortin family with characteristic biological activities, were purified to homogeneity from single human pituitary glands and chemically identified. Isolation of the peptides was based on size fractionation by Sephadex G-75 chromatography followed by two HPLC steps using reverse-phase and paired-ion reverse-phase systems and was monitored by radioimmunoassay. During the isolation procedure alpha- and gamma-endorphin-sized material behaved chromatographically and immunologically indistinguishably from synthetic alpha- and gamma-endorphin. The amino acid composition and NH2-terminus of isolated peptides demonstrated their identity as authentic alpha-endorphin and gamma-endorphin. Acetylated forms were absent. In addition, evidence is provided that large forms with alpha- and gamma-endorphin immunoreactivity detected during gel filtration are human lipotropin-(1-74) and -(1-75), respectively. The data substantiate that alpha-endorphin and gamma-endorphin exist as endogenous peptides in the human pituitary gland.
Asunto(s)
Endorfinas/aislamiento & purificación , Hipófisis/análisis , Aminoácidos/análisis , Cromatografía en Gel/métodos , Cromatografía Líquida de Alta Presión/métodos , Humanos , Radioinmunoensayo , alfa-Endorfina , gamma-EndorfinaRESUMEN
The timing and occurrence of the preovulatory luteinizing hormone (LH) surge in the female rodent are critically dependent on the integrity of the suprachiasmatic nucleus (SCN). Destruction of the SCN leads to a cessation of the ovarian cycle, whereas implantation of estrogen in ovariectomized rats results in daily LH surges. The anatomical substrate for these effects is not known. Previous studies involving lesions of the SCN have suggested the presence of a direct vasoactive intestinal polypeptide (VIP)-containing pathway to gonadotropin-releasing hormone (GnRH) neurons. To further investigate the direct connection between the SCN and the GnRH system, we have used tract-tracing with the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PhaL) in combination with an immunocytochemical staining for GnRH in light and electron microscopic studies. Small, unilateral PhaL deposits, especially when they were placed in the rostral ventrolateral portion of the SCN, revealed a bilateral projection to the preoptic area, where PhaL-immunoreactive fibers were regularly found in close apposition to GnRH neurons. Ultrastructural studies showed synaptic interaction of PhaL-containing fibers with GnRH-immunoreactive (IR) cell bodies, thus demonstrating a direct SCN-GnRH connection. Taken together, these data provide evidence for the existence of a monosynaptic pathway from the SCN to the GnRH system in the hypothalamus of the female rat. We suggest that this pathway may contain at least VIP as a putative transmitter and may play a role in the circadian regulation of the estrous cycle in the female rat.
Asunto(s)
Hormona Liberadora de Gonadotropina/metabolismo , Vías Nerviosas/ultraestructura , Núcleo Supraquiasmático/ultraestructura , Animales , Mapeo Encefálico , Femenino , Hipotálamo/ultraestructura , Inmunohistoquímica , Microscopía Electrónica , Neuronas/ultraestructura , Ratas , Ratas Sprague-Dawley , Núcleo Supraquiasmático/fisiologíaRESUMEN
The bed nucleus of the stria terminalis (BNST) is involved in autonomic and behavioral reactions to fearful stimuli and contains corticotropin-releasing hormone (CRH) fibers and terminals. The role of CRH in the medial part of the BNST in the regulation of heart rate (HR) and PQ interval of the electrocardiogram was studied under resting conditions and conditioned fear stress in freely moving rats. Microinfusion of CRH (0.2 microg/0.6 microl) in the medial BNST under resting conditions significantly enhanced HR as compared to saline treatment, but did not reduce the PQ interval, indicating that exogenous CRH in the medial BNST can activate both the sympathetic and parasympathetic cardiac outflow. In addition, CRH induced a slight increase in gross locomotor activity, an effect that succeeded the tachycardiac response, indicating that the HR response was not a consequence of increased locomotor activity, but likely a direct effect of CRH. CF was induced by 10-min forced exposure to a cage in which the rat had experienced footshocks (5 x 0.5 mA x 3s) the day before. alpha-helical CRH(9-41) (alphahCRH; 5 microg/0.6 microl), a non-selective CRH receptor antagonist, or saline was infused into the medial BNST of rats prior to CF. CF induced freezing behavior, associated with an increase in HR and PQ interval, indicating activation of sympathetic and vagal outflow to the heart. alphahCRH significantly reduced the PQ response, but enhanced the tachycardia, suggesting inhibition of vagal activity. In addition, alpha-helical CRH(9-41) reduced the freezing response. Taken together, the data provide first evidence that CRH, released in the medial BNST during stress, contributes to cardiac stress responses, particularly by activating vagal outflow.
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Hormona Liberadora de Corticotropina/metabolismo , Corazón/inervación , Vías Nerviosas/efectos de los fármacos , Neuronas/efectos de los fármacos , Núcleos Septales/efectos de los fármacos , Estrés Fisiológico/fisiopatología , Sistema Nervioso Simpático/efectos de los fármacos , Nervio Vago/efectos de los fármacos , Animales , Condicionamiento Psicológico/fisiología , Estado de Conciencia/fisiología , Hormona Liberadora de Corticotropina/farmacología , Electrocardiografía/efectos de los fármacos , Miedo/fisiología , Corazón/fisiología , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Masculino , Actividad Motora/efectos de los fármacos , Actividad Motora/fisiología , Vías Nerviosas/citología , Vías Nerviosas/metabolismo , Neuronas/citología , Neuronas/metabolismo , Ratas , Ratas Wistar , Núcleos Septales/citología , Núcleos Septales/metabolismo , Sistema Nervioso Simpático/citología , Sistema Nervioso Simpático/metabolismo , Nervio Vago/fisiologíaRESUMEN
Mentally healthy subjects show increased plasma concentrations of the neuropeptides, arginine vasopressin (AVP) and oxytocin (OT), under conditions of stress, but data are lacking about plasma concentrations of AVP and OT in patients with major depression. We thus assessed plasma concentrations of AVP and OT in patients with major depression (n = 52) and healthy controls (n = 37). Mean plasma AVP concentrations were higher in the group of depressed patients than in controls. A subgroup of 16 patients showed very high levels of plasma AVP, but no other feature differentiating this subgroup from the other patients was found. In-patients showed higher plasma AVP levels than out-patients, and melancholic patients had higher plasma AVP levels than did nonmelancholic patients. Plasma AVP levels were slightly related to psychomotor retardation and significantly inversely to neuroticism. Patients' plasma OT concentrations had a wider range than in controls. AVP and AVP-mediated functions may be a factor in the clinical picture of depression, possibly by influencing the activity of the hypothalamic-pituitary-adrenal axis.
Asunto(s)
Arginina Vasopresina/sangre , Trastorno Depresivo/sangre , Hormona Adrenocorticotrópica/sangre , Adulto , Anciano , Trastorno Depresivo/fisiopatología , Trastorno Depresivo/psicología , Femenino , Humanos , Hidrocortisona/sangre , Sistema Hipotálamo-Hipofisario/fisiopatología , Masculino , Persona de Mediana Edad , Concentración Osmolar , Oxitocina/sangre , Personalidad , Escalas de Valoración Psiquiátrica , Sodio/sangreRESUMEN
The involvement of the corticotropin-releasing hormone (CRH) type 1 receptor in CRH-induced cardiac responses was studied in freely moving rats. Intracerebroventricular (icv) infusion of 2 microg CRH under resting conditions resulted in a significant increase in heart rate (HR), but did not significantly affect the PQ interval of the electrocardiogram. This effect involves sympathetic nervous system (SNS) activation, since CRH-treatment resulted in a marked increase in plasma norepinephrine (NE) and epinephrine (E), and sympathetic blockade by subcutaneously injected atenolol (1 mg/kg), a beta1-selective adrenergic antagonist, completely prevented the CRH-induced tachycardia. CRH infusion after sympathetic blockade resulted in an elongation of the PQ interval, indicating CRH-induced vagal activation. Gross locomotor activity (GA) was determined to study its possible indirect effects on cardiac activity. Although CRH induced a marked increase in GA, this effect followed the tachycardiac response, indicating that the HR response was not a consequence of increased locomotor activity, but was a direct effect of icv CRH. Treatment with CP-154,526 (icv, 10 or 25 microg), a selective CRH type 1 receptor antagonist, did not affect baseline HR, plasma NE and E, whereas it partially blocked the CRH-induced increase in HR, plasma NE and E levels. CP-154,526 treatment had no significant effects on baseline or CRH-induced changes in GA. These results indicate that CRH activates the sympathetic nervous system at least in part via the CRH type 1 receptor.
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Sistema Nervioso Autónomo/efectos de los fármacos , Sistema Nervioso Autónomo/fisiología , Hormona Liberadora de Corticotropina/farmacología , Receptores de Hormona Liberadora de Corticotropina/fisiología , Antagonistas Adrenérgicos beta/farmacología , Animales , Atenolol/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Masculino , Actividad Motora/efectos de los fármacos , Actividad Motora/fisiología , Sistemas Neurosecretores/efectos de los fármacos , Sistemas Neurosecretores/fisiología , Pirimidinas/farmacología , Pirroles/farmacología , Ratas , Ratas WistarRESUMEN
beta-Endorphin is the putative precursor molecule of gamma- and alpha-endorphin. To investigate whether long-term changes in the activity of cells producing beta-endorphin are paralleled by alterations in the enzymatic processing of beta-endorphin, the effects of chronic treatment of rats with dopamine (DA) receptor ligands were examined on the content of immunoreactivity of beta-, gamma- and alpha-endorphin of dissected regions of the pituitary gland and the brain. Treatment with the DA receptor antagonist, haloperidol, resulted in a significant increase in the concentration of immunoreactivity for beta-, gamma-, and alpha-endorphin in the neurointermediate lobe, and of beta-endorphin in the anterior lobe of the pituitary gland. Levels of immunoreactivity of alpha-melanotropin and beta-endorphin in plasma were elevated, but those of corticosterone were decreased. This indicates that, in the intermediate lobe, both the biosynthetic and the secretory activity of cells producing beta-endorphin had increased, whereas in the anterior lobe, the secretory activity of beta-endorphin cells had decreased. No effects were observed on the ratios beta-endorphin/gamma-endorphin and beta-endorphin/alpha-endorphin in the intermediate lobe. In the anterior lobe however, the ratio beta-endorphin/alpha-endorphin had significantly increased. The effects of chronic treatment with the DA receptor agonist, bromocriptine, on levels of hormones in pituitary and plasma were opposite to those induced by haloperidol. In the brain, treatment with haloperidol selectively increased the content of immunoreactivity for beta-, gamma- and alpha-endorphin of the hypothalamus and the hippocampus and did not affect levels of peptides in the other regions of the brain studied.(ABSTRACT TRUNCATED AT 250 WORDS)
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Encéfalo/metabolismo , Bromocriptina/farmacología , Endorfinas/metabolismo , Haloperidol/farmacología , Hipófisis/metabolismo , betaendorfina/metabolismo , Animales , Encéfalo/efectos de los fármacos , Masculino , Hipófisis/efectos de los fármacos , Radioinmunoensayo , Ratas , Ratas Endogámicas , alfa-Endorfina , gamma-EndorfinaRESUMEN
Endogenous opioids have been implicated in the neurobiological mechanisms underlying drug addiction. Although some information is available concerning effects of abused drugs on the endogenous opioid systems, the interpretation of these effects is hampered because data on the actual changes in the endogenous opioids during the dynamics of the drug addiction are lacking. The present report deals with changes in endogenous opioid activity before and after the daily self-administration session in rats offered cocaine or ethanol, using an in vivo autoradiographic receptor occupancy procedure. In separate saline-controlled experiments drug-naive rats were allowed to intravenously self-administer cocaine (30 microg/infusion) and ethanol (0.05%) for five consecutive daily sessions of 6 h. Immediately following the last session on day 5 or just before a scheduled next daily session on day 6, the rats were injected with [3H]diprenorphine and subsequently prepared for autoradiography. Decreased [3H]diprenorphine binding was observed throughout the subcortical brain after the daily session in cocaine, but hardly in animals self-administering ethanol. These changes are thought to reflect a direct or an indirect effect of the drug on endogenous opioid systems. Before the daily session, the [3H]diprenorphine binding was decreased in restricted areas of the mesocorticolimbic system and of the thalamus in both cocaine and ethanol self-administering animals. These data suggest that release of endogenous opioids at the time the desire for cocaine or ethanol is high, which may be pertinent for drug-induced craving and relapse of drug addicts.
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Alcoholismo/metabolismo , Encéfalo/metabolismo , Trastornos Relacionados con Cocaína/metabolismo , Cocaína/administración & dosificación , Diprenorfina/farmacocinética , Endorfinas/metabolismo , Etanol/administración & dosificación , Animales , Autorradiografía/métodos , Infusiones Intravenosas , Sistema Límbico/metabolismo , Masculino , Especificidad de Órganos , Ratas , Ratas Wistar , Autoadministración , Tálamo/metabolismo , TritioRESUMEN
The luteinizing hormone surge in the female rat is the result of the integration of multiple signals within the medial preoptic area. The medial preoptic area contains gonadotropin-releasing hormone neurons that are responsible for the release of luteinizing hormone, neurons containing estrogen receptors and terminals originating from the suprachiasmatic nucleus with, for example, vasopressin as neurotransmitter. Both the medial preoptic area and suprachiasmatic nucleus are crucial for the occurrence of luteinizing hormone surges, since lesioning of either nucleus prevents pre-ovulatory and steroid-induced luteinizing hormone surges. In this study, we investigated whether vasopressin in the medial preoptic area could be the daily neuronal signal from the suprachiasmatic nucleus responsible for the timing of the luteinizing hormone surge. Vasopressin (50 ng/microl) or Ringer solution was administered by reverse microdialysis from Zeitgeber times 7.5 to 12.5 into the medial preoptic area of ovariectomized, estradiol-treated rats. The suprachiasmatic nucleus was lesioned to remove all cyclic luteinizing hormone secretion. This was evaluated by monitoring behavioral activity; animals that were arrhythmic were included in the experiments. Hourly blood samples were taken to measure plasma luteinizing hormone levels. Preoptic vasopressin administration induced a surge-like luteinizing hormone pattern in suprachiasmatic nucleus-lesioned animals, whereas constant, basal luteinizing hormone levels were found in the control animals. These data show that vasopressin, by itself, is able to trigger the luteinizing hormone surge in suprachiasmatic nucleus-lesioned rats. We propose that vasopressin is a timing signal from the suprachiasmatic nucleus responsible for the activation of the hypothalamo-pituitary-gonadal axis in the female rat.