RESUMO
BACKGROUND: The functional profile of cytomegalovirus (CMV)-specific CD8(+) T cells that associate with protection from and control of CMV DNAemia in allogeneic stem cell transplant (allo-SCT) recipients remains incompletely characterized. METHODS: We enumerated pp65 and immediate early (IE)-1-specific CD8(+) T cells expressing interferon-gamma, tumor necrosis factor-alpha, and CD107a, by flow cytometry in 94 patients at days +30 and +60 after allo-SCT. RESULTS: Fifty of 94 patients had CMV DNAemia within the first 100 days after transplant. CMV-specific CD8(+) T-cell responses (of any functional type) were more likely to be detected in patients who did not display CMV DNAemia than in those who did (P = 0.04). Qualitatively, no major differences in the functional signature of CMV-specific CD8(+) T cells were noted between patients who had or did not have CMV DNAemia. Patients displaying levels of polyfunctional CD8(+) T cells at day +30 >0.30 cell/µL had a lower risk of CMV DNAemia (positive predictive value 76%, and negative predictive value 43%). CONCLUSION: The presence of polyfunctional CD8(+) T cells (either expressing CD107a or not) was associated with lower levels of CMV replication, and higher frequency of self-resolved episodes. The data reported further clarify the role of polyfunctional CD8(+) T cells in control of CMV DNAemia in allo-SCT recipients.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , DNA Viral/sangue , Fosfoproteínas/metabolismo , Transplante de Células-Tronco/efeitos adversos , Proteínas da Matriz Viral/metabolismo , Adolescente , Adulto , Idoso , Linfócitos T CD8-Positivos/metabolismo , Estudos de Coortes , Citomegalovirus/genética , Citomegalovirus/metabolismo , Infecções por Citomegalovirus/virologia , Feminino , Humanos , Interferon gama/imunologia , Interferon gama/metabolismo , Masculino , Pessoa de Meia-Idade , Fosfoproteínas/imunologia , Transplante Homólogo/efeitos adversos , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Proteínas da Matriz Viral/imunologia , Adulto JovemRESUMO
BACKGROUND: This study aimed to characterize the dynamics of acquisition of cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) in CMV donor positive/recipient negative solid organ transplant (SOT) patients receiving long-term antiviral prophylaxis, and to determine whether development of CMI confers protection against CMV disease. METHODS: A prospective multicenter study was conducted in Spain from September 2009 to September 2012. Whole blood specimens were prospectively collected at 30, 90, 120, 200, and 365 days after SOT, and CMI was determined by enumeration of CMV pp65 and IE-1-specific CD69(+) /interferon-γ-producing CD8(+) and CD4(+) T cells by flow cytometry for intracellular cytokine staining. As part of a simultaneous clinical trial, patients received either early prophylaxis (in the first 3 days after transplantation) in the first period of the study or delayed prophylaxis (initiated at day 14) during the second period of the study. The impact of the dynamics of acquisition of CMV-specific CMI on the incidence of CMV disease was evaluated by Kaplan-Meier survival analysis. RESULTS: A total of 95 SOT recipients were recruited. CMV infection and disease occurred in 38 (40%) and 26 (27.4%) patients, respectively. The proportion of patients achieving any detectable CMV-specific CMI response at each of the different monitoring points was higher in liver transplant recipients, as compared to kidney or heart transplant recipients. The presence of any detectable response at day 120 or 200 was protective against the development of CMV disease (positive predictive values 92% and 93%, respectively). CONCLUSIONS: The rate of acquisition of CMV-specific CMI in SOT recipients undergoing antiviral prophylaxis differed significantly between different SOT populations. Patients developing any detectable CMI response were protected against the occurrence of CMV disease.
Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/prevenção & controle , Citomegalovirus/imunologia , Ganciclovir/análogos & derivados , Imunidade Celular , Transplante de Órgãos , Complicações Pós-Operatórias/prevenção & controle , Adulto , Idoso , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Feminino , Seguimentos , Ganciclovir/uso terapêutico , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios/métodos , Complicações Pós-Operatórias/imunologia , Complicações Pós-Operatórias/virologia , Estudos Prospectivos , Resultado do Tratamento , ValganciclovirRESUMO
OBJECTIVE: Previous studies on monitoring of post-transplant cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) are limited by single-centre designs and disparate risk categories. We aimed to assess the clinical value of a regular monitoring strategy in a large multicentre cohort of intermediate-risk kidney transplant (KT) recipients. METHODS: We recruited 124 CMV-seropositive KT recipients with no T-cell-depleting induction pre-emptively managed at four Spanish institutions. CMV-specific interferon-γ-producing CD4+ and CD8+ T cells were counted through the first post-transplant year by intracellular cytokine staining after stimulation with pp65 and immediate early-1 peptides (mean of six measurements per patient). The primary outcome was the occurrence of any CMV event (asymptomatic infection and/or disease). Optimal cut-off values for CMV-specific T cells were calculated at baseline and day 15. RESULTS: Twelve-month cumulative incidence of CMV infection and/or disease was 47.6%. Patients with pre-transplant CMV-specific CD8+ T-cell count <1.0 cells/µL had greater risk of CMV events (adjusted hazard ratio (aHR) 2.84; p 0.054). When the CMI assessment was performed in the immediate post-transplant period (day 15), the presence of <2.0 CD8+ T cells/µL (aHR 2.18; p 0.034) or <1.0 CD4+ T cells/µL (aHR 2.43; p 0.016) also predicted the subsequent development of a CMV event. In addition, lower counts of CMV-specific CD4+ (but not CD8+) T cells at days 60 and 180 were associated with a higher incidence of late-onset events. CONCLUSIONS: Monitoring for CMV-specific CMI in intermediate-risk KT recipients must be regular to reflect dynamic changes in overall immunosuppression and individual susceptibility. The early assessment at post-transplant day 15 remains particularly informative.
Assuntos
Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Transplante de Rim , Monitorização Imunológica/métodos , Linfócitos T/imunologia , Idoso , Feminino , Humanos , Imunidade Celular , Interferon gama/metabolismo , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Linfócitos T/citologia , Linfócitos T/metabolismo , TransplantadosRESUMO
OBJECTIVES: Evaluate the protective effect against late CMV disease of delaying antiviral prophylaxis initiation in D+/R- patients receiving solid organ transplant (SOT). METHODS: Prospective multicenter study in D+/R- SOT recipients in Spain (Sept/09-Sept/12). Whole blood specimens were prospectively collected after Tx for CMV-specific cell-mediated immunity (CMI) determination. Two prophylaxis strategies were compared: early prophylaxis (EP; starting within the first 3 days after Tx) and delayed prophylaxis (DP; starting 14 days after Tx). Risk factors for the occurrence of CMV disease were determined by survival analysis and proportional risk Cox regression models. RESULTS: We included 95 patients (50 EP V 45 DP). Twenty six patients (27.4%) developed CMV disease: 32.7% EP vs. 20% DP; (p = 0.2). No cases of CMV disease were reported previously to beginning delayed prophylaxis. The percentage of individuals with detectable CMI response was higher in patients with DP although differences did not reach statistic significance (42% vs 29.6% at day 200 after Tx; p = 0.4). There was a clear trend towards less end-organ CMV disease in patients receiving DP (18.2% EP vs 5% DP; p = 0.09) and DP was the only protective factor in the multivariate analysis (HR: 0.26; CI: 0.05-1.2; p = 0.09). CONCLUSIONS: A 14-day delay in CMV prophylaxis in D+/R- SOT recipients is safe and may reduce the incidence of late CMV end-organ disease although correlation of this effect with CMI responses was not complete.
Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/prevenção & controle , Citomegalovirus/imunologia , Ganciclovir/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Transplantados , Citomegalovirus/efeitos dos fármacos , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/virologia , Feminino , Humanos , Imunidade Celular , Incidência , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologia , Análise de SobrevidaRESUMO
Contextual fear conditioning is an important behavioral paradigm for studying the neurobiology of learning and memory and the mnemonic function of the hippocampus. We suggest that research in this domain can profit by a better theoretical understanding of the processes that contribute to this phenomenon. To facilitate this understanding, we describe a theory which assumes that physical elements of a conditioning context represented in the brain as either (a) a set of independent features or (b) features bound into a conjunctive representation by the hippocampus which supports pattern completion. Conditioning produced by shocking a rat in a particular context, in principle, can be produced by strengthening connections between the feature representations and/or the conjunctive representation and basolateral region of the amygdala. We illustrate how this theory clarifies some of the complexities associated with the existing literature and how it can be used to guide future empirical work. We also argue that the mechanisms (conjunctive representations and pattern completion) that mediate the contribution the hippocampus makes to contextual fear conditioning are the same ones that enable the hippocampus to support declarative memory in humans.
Assuntos
Condicionamento Clássico/fisiologia , Medo/fisiologia , Modelos Psicológicos , Tonsila do Cerebelo/fisiologia , Animais , Aprendizagem por Associação/fisiologia , Condicionamento Clássico/efeitos dos fármacos , Agonistas GABAérgicos/farmacologia , Hipocampo/fisiologia , Rememoração Mental/fisiologia , Muscimol/farmacologiaRESUMO
Unitary response to visual (optokinetic), somesthetic (neck and limb) and vestibular stimulation were recorded from the Purkinje cell layer throughout most of the dorsal surface of the frog cerebellum. Simple spike activity in Purkinje cells and activity from cells without complex spikes were considered. Optokinetic responses (types I-III) were restricted to the dorsal rim and auricular lobes. Units were sensitive to very small velocity of optokinetic cylinder rotation (0.02-0.03 degrees/s) with peak sensitivity at about 1 degree/s. On the average an approximately linear relation of response amplitude to stimulus velocity was observed from 0.02 to 1 degree/s. The response progressively diminished above 1 degree/s to become very small at 30 degrees/s. Asymmetric response and silencing of firing during part of the cycle were nonlinearities observed with sinusoidal optokinetic stimulation in the range of 0.02-1 Hz, +/- 5-10 degrees (peak velocities 0.8-30 degrees/s). Somesthetic responses were recorded throughout most of the corpus cerebelli proper but the strongest input was to rostral regions. No somatotopic arrangement was found. Rather, convergence from more than one limb and neck was relatively common. Adaptation to successive cycles of stimulation was characteristic of somesthetic responses. Vestibular responses (type I-IV) were recorded throughout most of the explored area but the strongest input was to the dorsal rim and auricular lobes. From the analysis of unitary activity, the dorsal rim and auricular lobes are shown to be functionally linked to the vestibular and optokinetic systems whereas the explored part of the corpus is linked to the somesthetic and vestibular systems.
Assuntos
Córtex Cerebelar/fisiologia , Sensação/fisiologia , Vestíbulo do Labirinto/fisiologia , Percepção Visual/fisiologia , Animais , Mapeamento Encefálico , Extremidades/inervação , Pescoço/inervação , Vias Neurais/fisiologia , Nistagmo Fisiológico , Células de Purkinje/fisiologia , Rana catesbeianaRESUMO
Unitary responses to visual (optokinetic) and somesthetic (cutaneous and propioceptive ) stimulation were recorded from the Purkinje cell layer of the cerebellum of acute (up to 30 h) and chronic (30-90 days) bilaterially labyrinthectomized frogs. Simple spikes from Purkinje cells as well as activity from cells without complex spikes were considered in this paper. The properties of the response and the distribution (restricted to the dorsal rim and auricular lobes) of the units sensitive to optokinetic stimulation of labyrinthectomized frogs, both acute and chronic, were similar to those previously reported for normal animals. The properties of the responses to somesthetic neck and limb stimulation remained similar to those of normal animals. However, there was an increase in the number of units responsive to somesthetic stimulation within the dorsal half of the corpus cerebelli (including the dorsal rim), a region experimentally deprived of vestibular afferents, neck responsive units were 33% of the total in acutely and 61% in chronically labyrinthectomized animals (compared to 5% in normal). Limb responsive units were 49% in acute and 65% in chronic animals (compared to 12% in normal). A consequence of the increase in somesthetic input was convergence of optokinetic and somesthetic inputs at the level of single units within the dorsal rim, totally absent before the lesion. The results suggest that the somesthetic spinal input might substitute for at least some features of the vestibular input to the cerebellum in bilaterally labyrinthectomized frogs.
Assuntos
Orelha Interna/fisiologia , Células de Purkinje/fisiologia , Sensação/fisiologia , Percepção Visual/fisiologia , Potenciais de Ação , Animais , Mapeamento Encefálico , Extremidades/inervação , Pescoço/inervação , Nistagmo Fisiológico , Rana catesbeianaRESUMO
The intra dorsal raphe nucleus (DRN) administration of corticotropin releasing hormone (CRF) inhibits serotonergic (5-HT) activity in this structure, an effect blocked by antagonists selective for the type 1 CRF receptor (CRF1). The DRN has a high density of the type 2 receptor (CRF2), and so the present experiments explored the impact of CRF2 activation within the DRN on 5-HT function. The intra-DRN administration of the selective CRF2 agonist urocortin 2 (Ucn 2) dose dependently increased 5-HT efflux in the basolateral amygdala, a projection region of the DRN. Intra-DRN Ucn 2 also increased c-fos expression in labeled 5-HT neurons. Both of these effects of Ucn 2 were completely blocked by intra-DRN antisauvagine-30 (ASV-30), a relatively selective CRF2 antagonist. These data suggest that CRF1 and CRF2 activation within the DRN affect 5-HT neurons in opponent fashion. Implications of these results for understanding the behavioral effects of CRF and other CRF-like ligands are discussed.
Assuntos
Tonsila do Cerebelo/metabolismo , Hormônio Liberador da Corticotropina/antagonistas & inibidores , Hormônio Liberador da Corticotropina/farmacologia , Núcleos da Rafe/efeitos dos fármacos , Serotonina/metabolismo , Tonsila do Cerebelo/anatomia & histologia , Tonsila do Cerebelo/efeitos dos fármacos , Animais , Contagem de Células/métodos , Diagnóstico por Imagem/métodos , Relação Dose-Resposta a Droga , Interações Medicamentosas , Espaço Extracelular/efeitos dos fármacos , Imuno-Histoquímica/métodos , Masculino , Microdiálise/métodos , Microinjeções/métodos , Fragmentos de Peptídeos/farmacologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Núcleos da Rafe/metabolismo , Ratos , Fatores de Tempo , UrocortinasRESUMO
In this work we report the existence of several evaginations extending out of the third ventricle within the mediobasal hypothalamus of the rat. In coronal sections, these evaginations appear as very narrow canaliculi integrating a canalicular system, which increases the contact surface between the ventricular lining and the nervous tissue. Consequently these evaginations enlarge the ventricular route for the transport of active principles present in the cerebrospinal fluid, such as (neuro)hormones and neurotransmitters. The mediobasal hypothalamus includes the arcuate nucleus and the median eminence (both involved in neuroendocrine mechanisms and in the regulation of pituitary function). A possible implication of our finding is that the neuroactive substance-containing ventricular cerebrospinal fluid may reach the intercellular spaces of the surrounding neuropil of the arcuate nucleus. According to literature these substances cross the ependyma of the lateral wall of the infundibular recess of the third ventricle. We suggest that such substances might also pass through the ependymal lining of the canalicular system, which displays the same ultrastructural characteristics as the rest of the ependyma of the lateral wall of the third ventricle. Therefore, the arcuate neurons may be influenced not only by synaptic inputs (afferent fibers) but also by non-synaptic diffusion neurotransmission (by means of neuroactive substances present in the cerebrospinal fluid).
Assuntos
Ventrículos Cerebrais/anatomia & histologia , Ventrículos Cerebrais/fisiologia , Hipotálamo Médio/anatomia & histologia , Hipotálamo Médio/fisiologia , Animais , Núcleo Arqueado do Hipotálamo/anatomia & histologia , Núcleo Arqueado do Hipotálamo/fisiologia , Ventrículos Cerebrais/ultraestrutura , Líquido Cefalorraquidiano/fisiologia , Feminino , Hipotálamo Médio/ultraestrutura , Masculino , Microvilosidades/ultraestrutura , Modelos Neurológicos , Ratos , Ratos Sprague-DawleyRESUMO
We have performed an ultrastructural and quantitative study of granular filamentous bodies (GFBs) present in the cytoplasm of some arcuate nucleus neurons of rats of both sexes castrated at one month of age and sacrificed one or three months later, as well as untreated and sham-operated animals of the same ages. GFBs appear as round or ovoid cytoplasmic inclusions of granular-filamentous texture and generally lack a limiting membrane; their sizes vary from 0.7 to 2.8 microns (average 1.7 microns). GFBs are present more frequently in the perikarya, but they also occur in dendrites. In rats of both sexes castrated at one month of age and sacrificed three months later a noticeable finding was the presence of some giant GFBs, whose major axis could reach up to 6 microns. The nomenclature, the origin and the possible significance and function of GFBs are discussed.
Assuntos
Núcleo Arqueado do Hipotálamo/ultraestrutura , Grânulos Citoplasmáticos/ultraestrutura , Neurônios/ultraestrutura , Orquiectomia , Ovariectomia , Animais , Núcleo Arqueado do Hipotálamo/citologia , Feminino , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
In this study we describe the most relevant morphological features of the microglial reaction that takes place in the arcuate nucleus (AN) after neurotoxic injury induced by a single subcutaneous injection of monosodium glutamate (MSG) in neonatal rats. The time course of the reaction was evaluated by lectinhistochemistry. Microglial/macrophagic cells were labelled with the lectin obtained from Lycopersicon esculentum and with B4 isolectin from Griffonia simplicifolia. The microglial response was also studied by ultrastructural observations. The histochemical study revealed the presence of few reactive microglial cells at 6 h post-injection. These cells were intensely stained and had a globular morphology but contained no neuronal debris inside them when observed under the electron microscope. At 12 h post-injection, the number of microglial cells had increased and, at the same time, intense phagocytic activity was observed ultrastructurally. The microglial reaction peaked at 24 and 36 h post-injection, when the number of microglial/macrophagic cells was maximum, although the ultrastructural observations showed that at 36 h the amount of debris ingested by macrophages was decreased with respect to animals sacrificed at 24 h. Finally, at 4 days after neurotoxic injection the number and morphology of microglial cells were similar to those observed in the control rats. The ultrastructural study also revealed the existence of microglial cell mitosis in the territory of the AN together with a strong increase in the number of supraependymal cells resembling macrophages in the third ventricle during the lesion. Our data demonstrate that activated microglial cells initially extend throughout the damaged territory, but from 24-36 h onwards they are especially patent in the ventrolateral portions of the AN.
Assuntos
Núcleo Arqueado do Hipotálamo/efeitos dos fármacos , Microglia/efeitos dos fármacos , Neurotoxinas/farmacologia , Lectinas de Plantas , Glutamato de Sódio/farmacologia , Animais , Núcleo Arqueado do Hipotálamo/ultraestrutura , Lectinas/administração & dosagem , Lectinas/farmacologia , Masculino , Microglia/ultraestrutura , Neurotoxinas/administração & dosagem , Ratos , Ratos Sprague-Dawley , Glutamato de Sódio/administração & dosagemRESUMO
The morphological features of the ependymal surface and supraependymal elements of the fourth ventricle of the rat were examined by scanning electron microscopy (SEM) and by the transmission electron microscopy (TEM). The results confirm the following aspects: 1) The presence of supraependymal elements and microvilli in the ependymal territories, including the sites where the cilia completely cover the ependymal surface; 2) The existence of cilia with oval or spherical thickenings together with supraependymal bulbs similar in size to those of the larger ciliary swellings; 3) Identification of the long supraependymal fibres with intermittent fusiform dilations observed under the SEM with the nerve fibres seen under the TEM; 4) The existence of intraventricular axodendritic synapses.
Assuntos
Tronco Encefálico/ultraestrutura , Cerebelo/ultraestrutura , Epêndima/ultraestrutura , Animais , Cílios/ultraestrutura , Feminino , Masculino , Microscopia Eletrônica , Microscopia Eletrônica de Varredura , Microvilosidades/ultraestrutura , Ratos , Sinapses/ultraestruturaRESUMO
An electron-microscopic study was carried out on the median eminence of cats during post-natal development. From the moment of birth (observations performed 12 hours later) Herring bodies were seen in the fibrillary layer of the median eminence. At 45 days after birth, myelinated nerve fibres could be observed, some of them containing neurosecretory granules. The number of myelinated fibres in the median eminence increased with age and at 90 days some Herring bodies appeared surrounded by myelin sheaths; these mainly contained neurosecretory granules and a few mitochondria.
Assuntos
Sistema Hipotálamo-Hipofisário/citologia , Corpos de Inclusão/ultraestrutura , Eminência Mediana/ultraestrutura , Bainha de Mielina/ultraestrutura , Fibras Nervosas/ultraestrutura , Animais , Gatos , Grânulos Citoplasmáticos/ultraestrutura , Feminino , Masculino , Microscopia Eletrônica , Mitocôndrias/ultraestruturaRESUMO
In order to evaluate the importance of prolactin in the pathogenesis and clinical evolution of fibrocystic disease of the breast, serum prolactin levels were determined in 7 patients affected by this condition before and during treatment with a prolactin inhibitor, 2-Br-alpha-ergocryptine (CB-154). Serum prolactin levels were found to be low or normal before treatment. During treatment with CB-154 there was an improvement in all patients but 2. The results of the study do not allow any conclusion on the possible relation between serum prolactin levels and fibrocystic disease of the breast but they indicate that CB-154 may be useful for treating patients with this disorder.
Assuntos
Doenças Mamárias/tratamento farmacológico , Bromocriptina/uso terapêutico , Ergolinas/uso terapêutico , Prolactina/antagonistas & inibidores , Adolescente , Adulto , Doenças Mamárias/sangue , Ergolinas/farmacologia , Feminino , Humanos , Pessoa de Meia-Idade , Prolactina/sangueRESUMO
To study the biogenesis of estrogens by the fetoplacental unit in late pregnancy, dehydroepiandrosterone sulfate was injected directly into the fetus and maternal blood sampled at intervals for 2 hours thereafter. There was no increase of estrone, estradiol, or estriol concentration in the maternal circulation.
Assuntos
Desidroepiandrosterona , Estrogênios/sangue , Troca Materno-Fetal , Testes de Função Placentária/métodos , Feminino , Humanos , GravidezRESUMO
The effects of escapable and yoked inescapable electric tailshocks on extracellular levels of serotonin (5-HT) in the ventral hippocampus and dorsal periaqueductal gray (dPAG) were measured by in vivo microdialysis. Inescapable, but not escapable shock increased extracellular 5-HT in the ventral hippocampus relative to restrained controls. Basal levels of 5-HT were elevated 24 h after inescapable shock, and previously inescapably shocked subjects exhibited an exaggerated 5-HT response to 2 brief footshocks. In contrast, escapable, but not inescapable shock, increased extracellular 5-HT in the dPAG, increased basal 5-HT in the dPAG 24 h later, and led to an enhanced 5-HT response to subsequent brief footshock.
Assuntos
Hipocampo/metabolismo , Substância Cinzenta Periaquedutal/metabolismo , Serotonina/metabolismo , Estresse Fisiológico/metabolismo , Animais , Comportamento Animal/fisiologia , Espaço Extracelular/metabolismo , Desamparo Aprendido , Ácido Hidroxi-Indolacético/metabolismo , Masculino , Microdiálise , Ratos , Ratos Sprague-DawleyRESUMO
The effects of escapable and yoked inescapable electric tailshocks on extracellular levels of serotonin (5-HT) in the basolateral amygdala were measured by in vivo microdialysis. Inescapable, but not escapable, shock increased extracellular 5-HT in the amygdala relative to restrained controls. Basal levels of 5-HT were elevated 24 h after inescapable shock, and previously inescapably shocked subjects exhibited an exaggerated 5-HT response to two brief footshocks. Levels of extracellular 5-HIAA did not follow any particular pattern and were not correlated with the changes in 5-HT.
Assuntos
Tonsila do Cerebelo/metabolismo , Condicionamento Operante/fisiologia , Reação de Fuga/fisiologia , Serotonina/metabolismo , Estresse Fisiológico/metabolismo , Análise de Variância , Animais , Eletrochoque , Ácido Hidroxi-Indolacético/metabolismo , Masculino , Microdiálise , Ratos , Ratos Sprague-DawleyRESUMO
Previous research indicates that the serotonergic neurons of the caudal dorsal raphe nucleus (DRN) are activated to a greater degree by inescapable shock (IS) as compared to escapable shock (ES), causing a greater release of serotonin (5-HT) in the DRN and in target regions. This differential activation is necessary for the behavioral changes that occur after exposure to IS, but not to ES (i.e. learned helplessness/behavioral depression). Although the critical role of the DRN in learned helplessness is clear, the neural inputs to the caudal DRN which result in this selective activation are unknown. One structure that may be involved in the activation of the DRN and the induction of learned helplessness/behavioral depression is the habenular complex. In experiment 1, habenula lesions eliminated the differential rise in DRN extracellular 5-HT levels in response to IS and ES exposure by severely attenuating the rise in 5-HT for both groups. In experiment 2, sham operated and habenula lesioned rats were exposed to either ES, IS or no stress (home cage control; HCC). Twenty-four hours later, sham rats previously exposed to IS exhibited longer escape latencies as compared to both ES and HCC rats (i.e. learned helplessness). The habenular lesion eliminated the differences in escape latency between groups, thus eliminating the induction of learned helplessness/behavioral depression. These results suggest that the habenula is necessary for the differential activation of the DRN and the escape deficits produced by IS.