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Acné Vulgar/diagnóstico , Acné Vulgar/epidemiología , Intolerancia a la Lactosa/diagnóstico , Intolerancia a la Lactosa/epidemiología , Adulto , Distribución por Edad , Estudios de Cohortes , Comorbilidad , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medio Oeste de Estados Unidos/epidemiología , Prevalencia , Valores de Referencia , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Distribución por Sexo , Adulto JovenRESUMEN
This review focuses on the treatment options for adult female patients with acne. Acne in adult female patients may start during adolescence and persist or have an onset in adulthood. Acne has various psychosocial effects that impact patients' quality of life. Treatment of acne in adult women specifically has its challenges due to the considerations of patient preferences, pregnancy, and lactation. Treatments vary widely and treatment should be tailored specifically for each individual woman. We review conventional therapies with high levels of evidence, additional treatments with support from cohort studies and case reports, complementary and/or alternative therapies, and new agents under development for the treatment of patients with acne.
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Estrógenos/administración & dosificación , Etinilestradiol/administración & dosificación , Etinilestradiol/efectos adversos , Melanoma/inducido químicamente , Neoplasias Cutáneas/inducido químicamente , Adolescente , Adulto , Anticonceptivos Orales , Relación Dosis-Respuesta a Droga , Estrógenos/efectos adversos , Femenino , Humanos , Medio Oeste de Estados Unidos , Estudios Retrospectivos , Adulto JovenAsunto(s)
Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico , Rosácea/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Metaloproteinasas de la Matriz/metabolismo , Persona de Mediana Edad , Estudios Retrospectivos , Rosácea/enzimología , Estados Unidos , Población Urbana , Adulto JovenRESUMEN
BACKGROUND: Invasive melanoma, a lethal form of skin cancer, is the seventh most common cancer in women. Factors such as a history of indoor tanning or sunburn and a personal or family history of skin cancer increase a woman's risk of developing a melanoma. OBJECTIVE: Because the majority of melanomas occur in patients age 40 years or older, which is the age that is recommended for women to begin screening mammograms, the mammogram experience could be used to promote early detection of melanoma by introducing skin self-examinations (SSE) to a population of women who are already invested in preventive health. METHODS: This was a pilot and feasibility study that was designed to promote the early detection of melanoma among women who undergo a mammogram at the Lynn Sage Breast Center at the Northwestern Medicine/Prentice Women's Hospital in Chicago, Illinois. The study was conducted in three phases: development of the materials, delivery of the program, and assessment of the program effectiveness. RESULTS: Eighty six percent of women with scheduled mammogram appointments participated in the study (n = 560). Among these women, 68% noticed the SSE information in the changing rooms, 78% thought the information applied to them, and 68% identified with at least one of the risk factors for melanoma. Twenty percent of the patients checked their skin in the changing room, 13% noticed a concerning mole, and 60% of those women who noted a concerning lesion stated their intent to see a dermatologist for further evaluation. CONCLUSION: A large proportion of the women in our study had risk factors for developing a melanoma and noticed the SSE information in the screening center. Placing an intervention to encourage methods for the early detection of melanoma in an outpatient mammography environment is an effective strategy to increase awareness in a large proportion of at-risk women.
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Carcinoma Basocelular/epidemiología , Carcinoma de Células Escamosas/epidemiología , Neoplasias Cutáneas/epidemiología , Tetraciclinas/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Basocelular/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Estudios de Casos y Controles , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medio Oeste de Estados Unidos , Neoplasias Cutáneas/diagnóstico , Adulto JovenRESUMEN
The mode of action of ribavirin is not completely understood. Ribavirin monotherapy has a measurable antiviral effect, which shows great variability. It might lead to an earlier steady state of plasma concentration and therefore enhance the effect of following combination treatment. The aim of this study was to evaluate the antiviral effect of ribavirin priming and its influence on sustained virologic response after combination treatment in a group of patients with different hepatitis C virus (HCV) types with or without prior treatment experience. Retrospective analysis of 75 patients (37 treatment naïve, 20 prior relapse, 16 prior nonresponse, genotype 1 present in 60 patients) from five centres who received ribavirin priming as part of an individual strategy in order to improve treatment outcome. All patients received ribavirin monotherapy with a mean dose of 14.5 mg kg-1 body weight for a mean of 28 days. After ribavirin priming, dual combination treatment with pegylated interferon alfa and ribavirin was started. The mean HCV RNA decline after ribavirin priming was 0.6 log10 IU mL-1 (P<.001). The initial viral decline depended on HCV type and previous treatment status being highest among prior relapsers (0.8 log10 IU mL-1 ; P=.002) and HCV type 2/3 (1.2 log10 IU mL-1 ; P=.05) and lowest among those with prior nonresponse (0.3 log10 IU mL-1 , P=.01). IFNL4 (formerly IL28B) genotype for rs12979860 and IFNL3 genotype rs8099917 did not influence the initial viral decline. The study demonstrates a significant variability in the viral dynamics and antiviral efficacy of ribavirin monotherapy, which is mainly influenced by prior treatment status. The fact that the lowest response pattern was observed in prior nonresponder patients to pegylated interferon alfa plus ribavirin combination therapy can be taken as a hint that not only the individual interferon, but also the ribavirin sensitivity contributes significantly to the nonresponsive state.
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Antivirales/administración & dosificación , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Ribavirina/administración & dosificación , Carga Viral , Adulto , Anciano , Quimioterapia Combinada/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Respuesta Virológica Sostenida , Resultado del TratamientoRESUMEN
The perioperative use of anticoagulants in general thoracic surgery can be considered to be a "two-edged sword": the goal to minimise the risk of a thromboembolic episode is contrary to the ongoing effort of the surgeon to minimise the risk of intra- and postoperative blood loss. Dispositional factors such as excessive tobacco use are common for thoracic surgery patients and often lead to cardiovascular comorbidity which necessitates the use of anticoagulants or antiplatelet drugs. For deep venous thrombosis prophylaxis and for the indication and use of vitamin K antagonists or antiplatelet drugs it is proven in the literature that the risk profile of the patient and his/her classification in the appropriate risk group are of major importance. Through the individual risk profile of the patient it is possible to plan the appropriate perioperative anticoagulant therapy which will safely assist the surgeon and his/her patient during the peri- and postoperative phase on the knife-edge between blood loss and eminent thromboembolism. Unfortunately there are not enough existing data and published literature for evidence-based guidelines referring to the correct perioperative management for the new oral anticoagulants. Management algorithms are being recommended according to the multiple aspects of anticoagulant-treatment.
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Anticoagulantes/uso terapéutico , Atención Perioperativa/métodos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Procedimientos Quirúrgicos Torácicos , Tromboembolia/prevención & control , Factores de Edad , Algoritmos , Anticoagulantes/efectos adversos , Comorbilidad , Conducta Cooperativa , Alemania , Adhesión a Directriz , Estado de Salud , Humanos , Comunicación Interdisciplinaria , Inhibidores de Agregación Plaquetaria/efectos adversosRESUMEN
Incomplete suppression of hepatitis C virus (HCV) replication with persistence of minimal viremia (partial virologic response) leading to treatment failure can be observed in a significant proportion of HCV type 1-infected patients during antiviral therapy. Recently, high-dose intravenous silibinin has demonstrated strong antiviral activity against HCV. We were therefore interested in whether patients with partial virologic response can be rescued by the on-treatment addition of a short-term course of high-dose intravenous silibinin infusions. Twenty patients who failed to achieve a complete virologic response to different interferon-based regimens qualified for the rescue strategy and received 1400 mg/day silibinin infusions on two consecutive days. Complete viral suppression (below the limit of detection <6 IU/mL, TMA assay) could be induced in 13 of 20 patients within the first week after the short-term silibinin infusion, and all but one of them also remained HCV RNA negative during the subsequent follow-up period on continued peginterferon plus ribavirin treatment. In the remaining seven patients, no complete suppression could be achieved although four showed a significant HCV RNA reduction in response to silibinin. Silibinin infusions were generally well tolerated, and activation of abdominal peristalsis with nausea, diarrhoea and vomiting were the most prominent side effects. Of the twelve patients who exhibited a durable response to peginterferon and ribavirin treatment, three achieved an SVR, two achieved a week 12 SVR and four suffered a viral relapse. Three patients could not complete the assigned antiviral treatment with peginterferon alpha and ribavirin for nonvirological reasons. Short-term administration of high-dose intravenous silibinin might be an interesting approach to rescue patients with ongoing minimal residual viremia while on interferon-based therapy. These preliminary findings may stimulate further studies to evaluate more refined therapeutic strategies.
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Antioxidantes/administración & dosificación , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/tratamiento farmacológico , Silimarina/administración & dosificación , Adulto , Anciano , Antioxidantes/efectos adversos , Antivirales/administración & dosificación , Quimioterapia Combinada/métodos , Femenino , Humanos , Infusiones Intravenosas , Interferón-alfa/administración & dosificación , Masculino , Persona de Mediana Edad , Ribavirina/administración & dosificación , Silibina , Silimarina/efectos adversos , Resultado del Tratamiento , Viremia/tratamiento farmacológicoRESUMEN
Acute hepatitis E virus (HEV) infection is a self-limiting symptomatic or asymptomatic disease. However, as recently observed, it can manifest itself as chronic hepatitis in patients receiving solid organ transplants as well as in patients with HIV infection or severe hematologic disorders. Here, we describe the clinical course of a 73-year-old male patient in whom HEV transmission occurred after receiving a HEV-infected liver from a donor with occult HEV infection, whereby the patient had tested negative for HEV RNA and anti-HEV antibodies shortly before explantation. Anti-HEV IgG, IgM, and HEV RNA were detected in the first tested serum sample of the liver recipient obtained 150 days after liver transplantation and remained positive (earlier samples after OLT were not available). Liver cirrhosis developed within 15 months and the patient died of septic shock. Based on phylogenetic analyses of the donor and recipient's HEV strains, we were able to prove that the occult HEV infection was transmitted via the graft.
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Hepatitis E/transmisión , Trasplante de Hígado/efectos adversos , Anciano , Enfermedad Crónica , Hepatitis E/diagnóstico , Hepatitis E/virología , Virus de la Hepatitis E/genética , Virus de la Hepatitis E/aislamiento & purificación , Humanos , Cirrosis Hepática/etiología , Cirrosis Hepática/patología , Cirrosis Hepática/virología , Masculino , Filogenia , ARN Viral/genética , ARN Viral/aislamiento & purificación , Donantes de TejidosRESUMEN
Recurrent herpes labialis (RHL) is a common condition associated with the formation of vesicles around the mouth, often preceded by prodromal symptoms including tingling and burning. Treatment is targeted toward individual episodes, but in severe cases, suppressive therapy may be indicated. At present, no cure exists for this troublesome condition. The purpose of this article is to serve as a practical guide in the management of RHL by summarizing current treatments and discussing potential new therapies.
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Antivirales/uso terapéutico , Herpes Labial/tratamiento farmacológico , Administración Cutánea , Administración Oral , Antivirales/administración & dosificación , Antivirales/farmacología , Quimioterapia Combinada , Herpes Labial/virología , Humanos , Recurrencia , Índice de Severidad de la EnfermedadRESUMEN
According to the rule of Bunsen and Roscoe, a photochemical reaction is directly proportional to the total energy dose, irrespective of the time over which this dose is delivered. To date few studies have addressed the validity of this rule in experimental and applied photobiology. Most of these data point to the fact that the rule of reciprocity is invalid or of limited validity for many photobiological reactions. For UV-induced cell death, photocarcinogenesis, psoralen photochemistry, and the effects of low level laser radiation it has been shown that at a constant total dose, the intensity of the source is a major factor that determines quality and quantity of the response. In clinical photomedicine systematic investigations on the reciprocity of exposure time and radiation intensity are lacking. Such studies are urgently needed since it can be concluded from experimental evidence, that their results might lead to therapeutic regimens with an improved therapeutic index, i.e. maximized therapeutic efficacy with minimized adverse reactions.
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Fotobiología , Animales , Muerte Celular/efectos de la radiación , Fraccionamiento de la Dosis de Radiación , Relación Dosis-Respuesta en la Radiación , Humanos , Neoplasias Inducidas por Radiación/etiología , Terapia PUVA , Fotoquímica , Neoplasias Cutáneas/etiología , Rayos Ultravioleta/efectos adversosRESUMEN
BACKGROUND: The mechanism underlying the depressant effect of opioids on neuronal activity within the neocortex is still not clear. Three modes of action have been suggested: (1) inhibition by activation of postsynaptic potassium channels, (2) interaction with postsynaptic glutamate receptors, and (3) presynaptic inhibition of glutamate release. To address this issue, the authors investigated the effects of mu- and delta-receptor agonists on excitatory postsynaptic currents (EPSCs) and on membrane properties of neocortical neurons. METHODS: Intracellular recordings were performed in rat brain slices. Stimulus-evoked EPSCs mediated by different glutamate receptor subtypes were pharmacologically isolated, and opioids were applied by addition to the bathing medium. Possible postsynaptic interactions between glutamate and opioid receptors were investigated using microiontophoretic application of glutamate on neurons functionally isolated from presynaptic input. RESULTS: delta-Receptor activation by d-Ala2-d-Leu5-enkephalin (DADLE) reduced the amplitudes of EPSCs by maximum 60% in a naltrindole-reversible manner (EC50: 6-15 nm). In 30-40% of the neurons investigated, higher concentrations (0.1-1 micrometer) of DADLE activated small outward currents. The mu-receptor selective agonist d-Ala2-N-MePhe5-Gly5-ol-enkephalin (0.1-1 micrometer) depressed the amplitudes of EPSCs by maximum 30% without changes in postsynaptic membrane properties. In the absence of synaptic transmission, inward currents induced by microiontophoretic application of glutamate were not affected by DADLE. CONCLUSIONS: Activation of mu- and delta-opioid receptors depresses glutamatergic excitatory transmission evoked in neocortical neurons by presynaptic inhibition. A weak activation of a postsynaptic potassium conductance becomes evident only at high agonist concentrations. There is no evidence for a postsynaptic interaction between glutamate and opioid receptors.
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Antagonistas de Aminoácidos Excitadores/farmacología , Neocórtex/efectos de los fármacos , Neuronas/efectos de los fármacos , Receptores AMPA/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Receptores Opioides delta/fisiología , Receptores Opioides mu/fisiología , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Analgésicos Opioides/farmacología , Animales , Relación Dosis-Respuesta a Droga , Encefalina Ala(2)-MeFe(4)-Gli(5)/farmacología , Leucina Encefalina-2-Alanina/farmacología , Femenino , Antagonistas de Receptores de GABA-A , Antagonistas de Receptores de GABA-B , Ácido Glutámico/farmacología , Iontoforesis , Masculino , Naltrexona/farmacología , Antagonistas de Narcóticos/farmacología , Neocórtex/citología , Neocórtex/fisiología , Neuronas/fisiología , Ratas , Ratas Wistar , Receptores AMPA/fisiología , Receptores de GABA-A/fisiología , Receptores de GABA-B/fisiología , Receptores de N-Metil-D-Aspartato/fisiología , Receptores Opioides delta/agonistas , Receptores Opioides mu/agonistas , Sinapsis/efectos de los fármacos , Sinapsis/fisiología , Transmisión Sináptica/efectos de los fármacosRESUMEN
Intra- and extracellular recordings were performed to investigate the influence of local disinhibition of neocortical circuits on corticostriatal synaptic transmission. In rat brain slices with preserved corticostriatal connections, electrical stimulation of the neocortex elicited composed postsynaptic responses in neostriatal neurons consisting of glutamatergic excitatory postsynaptic potentials (EPSPs) and weakly expressed GABAA receptor-mediated inhibitory postsynaptic potentials (IPSPs). Following local application of the GABAA receptor antagonist bicuculline to the neocortex, neocortical neurons responded to intracortical stimulation with transient paroxysmal depolarizations. Simultaneously, the amplitude of neocortically evoked EPSPs recorded from neostriatal neurons was found to be enhanced without changes in duration. Similarly, the amplitude of IPSPs increased following disinhibition of neocortical circuits. In addition and in contrast to EPSPs, the duration of the IPSPs was found to be markedly prolonged. The results demonstrate that local disinhibition of neocortical neuronal circuits potentiates both excitatory and inhibitory synaptic transmission in striatal neurons. However, compared to AMPA receptor-mediated excitation, GABAA receptor-mediated inhibition becomes more efficient due to a marked prolongation of IPSPs. The pronounced augmentation of inhibition can be attributed to a strong activation of inhibitory interneurons within the striatum.
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Ácido Glutámico/fisiología , Neocórtex/fisiología , Neostriado/fisiología , Inhibición Neural/fisiología , Transmisión Sináptica/fisiología , Ácido gamma-Aminobutírico/fisiología , Animales , Bicuculina/farmacología , Antagonistas del GABA/farmacología , Técnicas In Vitro , Masculino , Neocórtex/citología , Neocórtex/efectos de los fármacos , Vías Nerviosas/fisiología , Neuronas/efectos de los fármacos , Neuronas/fisiología , Neuronas Aferentes/fisiología , Ratas , Ratas WistarRESUMEN
On the basis of cytochemical and morphologic differences, two classes of gamma-aminobutyric acidergic (GABAergic) interneurons expressing calcium-binding proteins have been identified in the striatum of adult animals: neurons expressing either parvalbumin (PV) or calretinin (CR). The function of these calcium-binding proteins is not clear, however, they are associated with distinct classes of inhibitory interneurons within the adult neostriatum. By using immunocytochemical techniques, we analyzed the postnatal maturation and the spatiotemporal distribution of PV- and CR-positive neurons in the rat neostriatum compared with a third class of interneurons characterized by the expression of the acetylcholine-synthesizing enzyme, choline acetyltransferase (ChAT). PV-positive cells appeared initially on postnatal day 9 in the lateral region of the striatum. During postnatal weeks 2 and 3, the numbers of PV-positive neurons increased, and this cell population spread progressively in a lateromedial direction. In contrast, CR-expressing neurons were present at birth. During the first few days after birth, the number of CR-immunoreactive cells increased, reaching a peak on postnatal day 5 before declining during the following 2 weeks. A mediolateral gradient was evident temporarily. ChAT-containing neurons were detectable at birth in the lateral striatum. During postnatal weeks 1 and 2, the neurons matured along a lateral-to-medial gradient. The results indicate that the maturation of striatal interneurons is regulated differentially during postnatal development, resulting in a distinct spatiotemporal genesis of phenotypes. The sequential expression of CR and PV suggests a stage-dependent development of subsets of inhibitory interneurons and, hence, the stage-dependent maturation of functionally distinct inhibitory circuits within the neostriatum.
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Interneuronas/química , Neostriado/química , Proteínas del Tejido Nervioso/análisis , Parvalbúminas/análisis , Proteína G de Unión al Calcio S100/análisis , Animales , Calbindina 2 , Colina O-Acetiltransferasa/análisis , Femenino , Inmunohistoquímica , Masculino , Neostriado/citología , Neostriado/crecimiento & desarrollo , Ratas , Ratas Wistar , Grabación en VideoRESUMEN
During whole-cell recordings from rat neostriatal neurons with Neurobiotin-filled patch-clamp electrodes, we observed markedly prolonged action potentials. Similar long-lasting action potentials were not detected when the tracer was omitted from the pipette solution. Resting membrane potential and input resistance remained unchanged in the presence of the tracer. The investigation of this effect revealed that Neurobiotin decreased the threshold for calcium spike generation probably by blocking a potassium conductance activated by depolarisation or by a direct action on calcium channels. The effect of Neurobiotin displayed a fast onset and was not observed during intracellular recordings using conventional microelectrodes.
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Biotina/análogos & derivados , Neostriado/efectos de los fármacos , Neuronas/efectos de los fármacos , Potenciales de Acción/efectos de los fármacos , Animales , Biotina/toxicidad , Microelectrodos , Neostriado/citología , Neostriado/fisiología , Neuronas/fisiología , Técnicas de Placa-Clamp/instrumentación , Ratas , Ratas WistarRESUMEN
The spatial distribution of stimulus-evoked excitation in the mouse neostriatum was investigated in vitro by using voltage-sensitive dyes and an optical multi-site recording system (laser scanning microscopy). The scanning area (880 x 830 microns) was positioned in the center of coronal neostriatal slices and records were taken simultaneously from up to 20 detection sites. Stimulus-induced optical signals were blocked by tetrodotoxin (TTX) and disappeared following removal of Ca2+ from the extracellular medium. Furthermore, these responses were inhibited by the glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) indicating that the evoked signals reflected mainly glutamatergic synaptic activity. Electrical stimulation at defined positions elicited characteristic spatial patterns of activity within the neostriatum. Stimulation of the medial subcortical white matter or stimulation at the dorsomedial corner or at the midpoint of the scanning area evoked synaptic activity at all recording sites. However, the largest response amplitudes were invariably observed in the ventrolateral part of the scanning area. In contrast, stimulation at the dorsolateral, ventrolateral or at the ventromedial corner induced synaptic responses which remained restricted to a relatively small area in close vicinity to the site of stimulation. The GABAA receptor antagonist bicuculline did not influence the pattern of activity distribution. However, in the presence of bicuculline, a N-methyl-D-aspartate (NMDA) receptor-mediated delayed signal component was observed which again was most pronounced in the ventrolateral part of the scanning area. These results, obtained in an in vitro slice preparation, demonstrate that spatially defined afferent activation of neostriatal neuronal circuits leads to a characteristic pattern of activity distribution within the neostriatum. Thus, our data complement observations from morphological investigations as well as from electrophysiological studies in vivo that suggest a functional compartmentalization of this brain area.
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Potenciales Evocados/fisiología , Neostriado/fisiología , Transmisión Sináptica/fisiología , Animales , Técnicas In Vitro , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
Using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease, we investigated the long-term effects of dopaminergic denervation on synaptic transmission in an in vitro slice preparation of the mouse neostriatum. In control mice, electrical stimulation elicited an antidromic potential (N1) followed by a synaptically mediated field potential (N2). In many slices, a third component (N3) was observed. Determination of the maximum stimulus intensities unveiled that in 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine-pretreated animals, the stimulus strength necessary to evoke a maximum N2 response was significantly higher compared to control mice. Furthermore, 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine-pretreatment led to a less frequent appearance and/or to a reduction in the amplitude of the N3 component. Application of glutamate receptor agonists and antagonists revealed two additional differences between normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-pretreated mice. (1) Comparison of the efficacy of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist 6-cyano-7-nitroquinoxaline-2, 3-dione demonstrated an increase in the inhibitory effect of 6-cyano-7-nitroquinoxaline-2,3-dione in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-pretreated mice. (2) In normal mice, removal of magnesium ions from the bathing solution invariably led to the appearance of late N-methyl-D-aspartate receptor-dependent synaptic components. There components were only slightly expressed or virtually absent in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-pretreated mice. The described differences between the electrophysiological and pharmacological properties of evoked field potentials in slices from normal and 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine-pretreated mice disappeared following blockade of GABAA receptor-dependent inhibition by bicuculline. In normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-pretreated mice, bicuculline did not influence the amplitude of the N2 component, but invariably unmasked late synaptic components mediated by glutamate receptors. However, the potentiating effect of bicuculline was significantly stronger in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-pretreated mice compared to the controls. In the presence of bicuculline, the frequency of occurrence of the N3 component was identical in both groups. Furthermore, the apparent efficiency of 6-cyano-7-nitroquinoxaline-2,3-dione was no longer different. Application of bicuculline in the absence of magnesium ions resulted in a similar disinhibition of N-methyl-D-aspartate receptor-dependent late components as observed in the controls in the absence of bicuculline. The data demonstrate that chronic dopaminergic denervation reduces glutamate receptor-dependent synaptic excitation in the mouse neostriatum. Since differences between normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-pretreated mice disappear in the presence of bicuculline, we conclude that this reduction in excitability is due to a potentiation of GABAA receptor-dependent inhibition.