RESUMO
Alterations in the state of excitability of midbrain dopamine (DA) neurons from the ventral tegmental area (VTA) may underlie changes in the synaptic plasticity of the mesocorticolimbic system. Here, we investigated norepinephrine's (NE) regulation of VTA DA cell excitability by modulation of the hyperpolarization-activated cation current, Ih, with whole cell recordings in rat brain slices. Current clamp recordings show that NE (40 microM) hyperpolarizes spontaneously firing VTA DA cells (11.23+/-4 mV; n=8). In a voltage clamp, NE (40 microM) induces an outward current (100+/-24 pA; n=8) at -60 mV that reverses at about the Nernst potential for potassium (-106 mV). In addition, NE (40 microM) increases the membrane cord conductance (179+/-42%; n=10) and reduces Ih amplitude (68+/-3% of control at -120 mV; n=10). The noradrenergic alpha-1 antagonist prazosin (40 microM; n=5) or the alpha-2 antagonist yohimbine (40 microM; n=5) did not block NE effects. All NE-evoked events were blocked by the D2 antagonists sulpiride (1 microM) and eticlopride (100 nM) and no significant reduction of Ih took place in the presence of the potassium channel blocker BaCl2 (300 microM). Therefore, it is concluded that NE inhibition of Ih was due to an increase in membrane conductance by a nonspecific activation of D2 receptors that induce an outward potassium current and is not a result of a second messenger system acting on h-channels. The results also suggest that Ih channels are mainly located at dendrites of VTA DA cells and, thus, their inhibition may facilitate the transition from single-spike firing to burst firing and vice versa.
Assuntos
Canais de Cátion Regulados por Nucleotídeos Cíclicos/fisiologia , Dopamina/fisiologia , Neurônios/fisiologia , Norepinefrina/fisiologia , Canais de Potássio/fisiologia , Área Tegmentar Ventral/fisiologia , Antagonistas Adrenérgicos alfa/farmacologia , Algoritmos , Animais , Compostos de Bário/farmacologia , Cloretos/farmacologia , Canais de Cátion Regulados por Nucleotídeos Cíclicos/antagonistas & inibidores , Interpretação Estatística de Dados , Antagonistas de Dopamina/farmacologia , Eletrofisiologia , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização , Masculino , Potenciais da Membrana/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Norepinefrina/farmacologia , Técnicas de Patch-Clamp , Prazosina/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores Adrenérgicos alfa/efeitos dos fármacos , Receptores Adrenérgicos alfa/fisiologia , Receptores de Dopamina D2/efeitos dos fármacos , Salicilamidas/farmacologia , Área Tegmentar Ventral/citologia , Área Tegmentar Ventral/efeitos dos fármacos , Ioimbina/farmacologiaRESUMO
This study quantifies the influence of shared household and kinship on egg counts during Schistosoma mansoni infection in a sample from rural Brazil. Detailed genealogic information allowed assignment of 597 individuals to 6 multihousehold pedigrees residing in 145 households. A variance component method was used to partition egg counts into shared household, additive genetic, and individual-specific environmental effects. Host additive genetic effects consistently accounted for a large proportion of the variation in egg counts: 43% in an unadjusted model and 40% in model adjusted for covariates. In a model that examined the confounding of shared household with kinship, additive genetic effects still accounted for 27% of the variation in egg counts and shared household only 12%. The consistently important role for host additive genetic factors on the variation in egg counts points to new ways of modeling and understanding the mechanisms that contribute to trait variation during infection with S. mansoni.
Assuntos
Fezes/parasitologia , Predisposição Genética para Doença , Contagem de Ovos de Parasitas , População Rural , Schistosoma mansoni/isolamento & purificação , Esquistossomose/parasitologia , Animais , Brasil/epidemiologia , Funções Verossimilhança , Esquistossomose/epidemiologia , Esquistossomose/fisiopatologiaRESUMO
The repeated use of psychostimulants in humans has been associated with progressive enhancement of anxiety, panic attacks, and eventually paranoid psychosis. The appearance of such behaviors has been termed behavioral sensitization, which forms part of the basic pathological mechanisms involved in drug addiction. Psychostimulants act via a circuit involving the ventral tegmental area (VTA), prefrontal cortex (PFC), and nucleus accumbens. The PFC sends glutamatergic projections that activate dopaminergic neurons in the VTA. These projections provide an extremely important excitatory drive necessary for the development of sensitization. The effects of cocaine administration on the response of dopaminergic VTA cells to activation of the PFC have not been reported. Here the effects of acute cocaine administration on VTA cell response to PFC stimulation are examined. Statistical analysis of the changes in spontaneous activity and evoked response revealed a significant decrease in spontaneous activity at 1.0 mg/kg i.v. after cocaine treatment compared to baseline levels. The net effect was an increase in signal-to-noise ratio. Treatment with MK-801 at a dose of 2 mg/kg showed that the excitatory response was, at least partially, NMDA-mediated. Prazosin pretreatment (0.5 mg/kg i.p.) did not prevent a significant decrease in spontaneous activity brought about by cocaine (15 mg/kg, i.p.). Nonetheless, prazosin alone induced a significant decrease in the response to PFC stimulation when compared to baseline. In addition, iontophoretic application of norepinephrine (NE) onto VTA cells revealed that NE potentiated (19.2%), enhanced (26.9%), or suppressed (46.2%) the glutamate-evoked response in VTA cells. The results suggest that a possible role of cocaine in the process of sensitization might be to amplify the PFC-induced excitation at the VTA. Since the iontophoretic release of NE in almost half of the sampled cells produced similar effects to those of cocaine it may suggest a possible NE-mediated mechanism for cocaine actions.
Assuntos
Cocaína/farmacologia , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia , Área Tegmentar Ventral/fisiologia , Animais , Cocaína/administração & dosagem , Estimulação Elétrica , Ácido Glutâmico/farmacologia , Injeções Intravenosas , Masculino , Neurônios/efeitos dos fármacos , Norepinefrina/farmacologia , Ratos , Ratos Sprague-Dawley , Área Tegmentar Ventral/efeitos dos fármacosRESUMO
A number of studies have pointed out the potential importance of the household in the transmission of schistosomiasis. The clustering of domestic activities associated with water collection, storage, and usage can result in the sharing of transmission sites and infective water contact behaviours. In this study, we employed a variance component method to estimate effects due to individual risk factors and shared residence on the variance in faecal egg counts during Schistosoma mansoni infection. A suite of covariates, which included demographic, socioeconomic, water supply, and water contact behaviour terms, contributed 15% to the variance in faecal egg counts. Shared residence alone accounted for 28% of the variance in faecal egg excretion. When both the suite of covariates and shared residence were considered in the same model, shared residence still contributed 22% to the variance in infection intensity. These results point to the importance of shared residence as a means of capturing the complex interrelationship between shared demographic, socioeconomic, physical environmental, and behavioural factors that influence transmission of schistosomiasis at the household level.
Assuntos
Características da Família , Comportamentos Relacionados com a Saúde , Saúde da População Rural , Esquistossomose mansoni/epidemiologia , Esquistossomose mansoni/transmissão , Água , Adolescente , Adulto , Análise de Variância , Brasil/epidemiologia , Criança , Pré-Escolar , Análise por Conglomerados , Doenças Endêmicas , Fezes/parasitologia , Feminino , Humanos , Higiene , Lactente , Masculino , Pessoa de Meia-Idade , Contagem de Ovos de Parasitas , Prevalência , Fatores de Risco , Esquistossomose mansoni/parasitologia , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
The genus Helcogrammoides comprises three species of small, cryptic shorefishes, H. antarcticus, H. chilensis, and H. cunninghami. All three species inhabit shallow water along exposed rocky coasts. Specimens reported herein extend the known distributions of H. chilensis and H. cunninghami to the vicinity of Lima, Peru, approximately 1600 km north of their previously reported northernmost records in Chile. Helcogrammoides chilensis and H. cunninghami occur sympatrically over most of their ranges in Peru and Chile and are frequently taken together in the same field collections. Lectotypes are designated for H. chilensis and H. cunninghami. Diagnoses and an identification key are provided for the species.
Assuntos
Perciformes/classificação , Animais , Chile , Feminino , Geografia , Masculino , Perciformes/anatomia & histologia , PeruRESUMO
Multilocus genotyping of microbial pathogens has revealed a range of population structures, with some bacteria showing extensive recombination and others showing almost complete clonality. The population structure of the protozoan parasite Plasmodium falciparum has been harder to evaluate, since most studies have used a limited number of antigen-encoding loci that are known to be under strong selection. We describe length variation at 12 microsatellite loci in 465 infections collected from 9 locations worldwide. These data reveal dramatic differences in parasite population structure in different locations. Strong linkage disequilibrium (LD) was observed in six of nine populations. Significant LD occurred in all locations with prevalence <1% and in only two of five of the populations from regions with higher transmission intensities. Where present, LD results largely from the presence of identical multilocus genotypes within populations, suggesting high levels of self-fertilization in populations with low levels of transmission. We also observed dramatic variation in diversity and geographical differentiation in different regions. Mean heterozygosities in South American countries (0.3-0.4) were less than half those observed in African locations (0. 76-0.8), with intermediate heterozygosities in the Southeast Asia/Pacific samples (0.51-0.65). Furthermore, variation was distributed among locations in South America (F:(ST) = 0.364) and within locations in Africa (F:(ST) = 0.007). The intraspecific patterns of diversity and genetic differentiation observed in P. falciparum are strikingly similar to those seen in interspecific comparisons of plants and animals with differing levels of outcrossing, suggesting that similar processes may be involved. The differences observed may also reflect the recent colonization of non-African populations from an African source, and the relative influences of epidemiology and population history are difficult to disentangle. These data reveal a range of population structures within a single pathogen species and suggest intimate links between patterns of epidemiology and genetic structure in this organism.