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2.
An Bras Dermatol ; 96(2): 188-195, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33640188

RESUMO

Pyoderma gangrenosum associated to the use of cocaine/levamisole is a rare condition associated to their consumption. Cocaine use is frequent in Colombia, and the substance is contaminated with levamisole, an anthelmintic that increases the psychotropic effects and enhances its side effects. We present three clinical cases of patients with ulcerated lesions, in which the diagnosis was pyoderma gangrenosum secondary to the use of cocaine contaminated with levamisole. This called the attention of the health staff to investigate the abuse of substances in gangrenous pyoderma and also evidence that the interruption of consumption was the basis of management.


Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Pioderma Gangrenoso , Cocaína/efeitos adversos , Transtornos Relacionados ao Uso de Cocaína/complicações , Colômbia , Humanos , Levamisol , Pioderma Gangrenoso/induzido quimicamente , Pioderma Gangrenoso/tratamento farmacológico
3.
Nat Biomed Eng ; 5(1): 64-76, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33483710

RESUMO

The detection and quantification of protein biomarkers in interstitial fluid is hampered by challenges in its sampling and analysis. Here we report the use of a microneedle patch for fast in vivo sampling and on-needle quantification of target protein biomarkers in interstitial fluid. We used plasmonic fluor-an ultrabright fluorescent label-to improve the limit of detection of various interstitial fluid protein biomarkers by nearly 800-fold compared with conventional fluorophores, and a magnetic backing layer to implement conventional immunoassay procedures on the patch and thus improve measurement consistency. We used the microneedle patch in mice for minimally invasive evaluation of the efficiency of a cocaine vaccine, for longitudinal monitoring of the levels of inflammatory biomarkers, and for efficient sampling of the calvarial periosteum-a challenging site for biomarker detection-and the quantification of its levels of the matricellular protein periostin, which cannot be accurately inferred from blood or other systemic biofluids. Microneedle patches for the minimally invasive collection and analysis of biomarkers in interstitial fluid might facilitate point-of-care diagnostics and longitudinal monitoring.


Assuntos
Biomarcadores/análise , Líquido Extracelular/química , Microtecnologia/instrumentação , Agulhas , Animais , Cocaína/análise , Citocinas/análise , Desenho de Equipamento , Feminino , Corantes Fluorescentes/química , Técnicas de Imunoadsorção/instrumentação , Limite de Detecção , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL
4.
Psychopharmacology (Berl) ; 238(4): 1059-1068, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33388819

RESUMO

RATIONALE: The probability of structural remodeling in brain circuits may be modulated by molecules of perineuronal nets (PNNs) that restrict neuronal plasticity to stabilize circuits. Animal research demonstrates that addictive drugs can remodel PNNs in different brain regions, including the cerebellum. OBJECTIVE: This study aimed to investigate the effects of short versus extended access to cocaine self-administration on PNN expression around Golgi interneurons in the cerebellar cortex after different periods of abstinence. METHODS: After 1 week of training (2 h/day), Sprague-Dawley rats self-administered cocaine daily for 20 days under short (ShA) or extended (LgA) access. PNN expression in the cerebellum was assessed after 1 day, 7 days, and 28 days of forced abstinence. PNNs were immunolabeled using Wisteria floribunda agglutinin (WFA) and captured by confocal microscopy. RESULTS: WFA intensity increased in PNN-bearing Golgi neurons over the abstinence period and a higher proportion of more intense PNNs were formed throughout the first month of abstinence. After the first 24 h of cocaine abstinence, however, we found a reduction in WFA intensity in the cerebellar cortex of rats with ShA to cocaine as compared to naïve animals. When comparing with naïve rats, LgA rats showed consistent PNN upregulation at 28 days of cocaine abstinence. CONCLUSIONS: Our results suggest that cocaine self-administration produces modifications in PNN that enhance conditions for synaptic plasticity in the cerebellar cortex. These modifications are revealed shortly after the cessation of drug intake but PNNs become more intense during protracted abstinence in the LgA group, pointing to the stabilization of drug-induced synaptic changes. These findings indicate that extended access to cocaine self-administration dynamically regulates conditions for plasticity in the cerebellum during abstinence.


Assuntos
Córtex Cerebelar/fisiopatologia , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Rede Nervosa/fisiopatologia , Síndrome de Abstinência a Substâncias/fisiopatologia , Animais , Cocaína , Interneurônios , Masculino , Plasticidade Neuronal , Ratos , Ratos Sprague-Dawley , Autoadministração
5.
Anal Chem ; 93(4): 2578-2588, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33432809

RESUMO

Surface-enhanced Raman scattering (SERS) is an ultrasensitive analytical technique, which is capable of providing high specificity; thus, it can be used for toxicological drug assay (detection and quantification). However, SERS-based drug analysis directly in human biofluids requires mitigation of fouling and nonspecificity effects that commonly appeared from unwanted adsorption of endogenous biomolecules present in biofluids (e.g., blood plasma and serum) onto the SERS substrate. Here, we report a bottom-up fabrication strategy to prepare ultrasensitive SERS substrates, first, by functionalizing chemically synthesized gold triangular nanoprisms (Au TNPs) with poly(ethylene glycol)-thiolate in the solid state to avoid protein fouling and second, by generating flexible plasmonic patches to enhance SERS sensitivity via the formation of high-intensity electromagnetic hot spots. Poly(ethylene glycol)-thiolate-functionalized Au TNPs in the form of flexible plasmonic patches show a twofold-improved signal-to-noise ratio in comparison to triethylamine (TEA)-passivated Au TNPs. Furthermore, the plasmonic patch displays a SERS enhancement factor of 4.5 ×107. Utilizing the Langmuir adsorption model, we determine the adsorption constant of drugs for two different surface ligands and observe that the drug molecules display stronger affinity for poly(ethylene glycol) ligands than TEA. Our density functional theory calculations unequivocally support the interaction between drug molecules and poly(ethylene glycol) moieties. Furthermore, the universality of the plasmonic patch for SERS-based drug detection is demonstrated for cocaine, JWH-018, and opioids (fentanyl, despropionyl fentanyl, and heroin) and binary mixture (trace amount of fentanyl in heroin) analyses. We demonstrate the applicability of flexible plasmonic patches for the selective assay of fentanyl at picogram/milliliter concentration levels from drug-of-abuse patients' blood plasma. The fentanyl concentration calculated in the patients' blood plasma from SERS analysis is in excellent agreement with the values determined using the paper spray ionization mass spectrometry technique. We believe that the flexible plasmonic patch fabrication strategy would be widely applicable to any plasmonic nanostructure for SERS-based chemical sensing for clinical toxicology and therapeutic drug monitoring.


Assuntos
Análise Espectral Raman/métodos , Cocaína/química , Fentanila/química , Toxicologia Forense/métodos , Ouro/química , Heroína/química , Humanos , Indóis/química , Limite de Detecção , Espectrometria de Massas , Nanopartículas Metálicas/química , Naftalenos/química , Preparações Farmacêuticas , Plasma
7.
Nat Commun ; 12(1): 182, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420090

RESUMO

Processing within the anterior cingulate cortex (ACC) is crucial for the patterning of appropriate behavior, and ACC dysfunction following chronic drug use is thought to play a major role in drug addiction. However, cortical pyramidal projection neurons can be subdivided into two major types (intratelencephalic (IT) and pyramidal tract (PT)), with distinct inputs and projection targets, molecular and receptor profiles, morphologies and electrophysiological properties. Yet, how each of these cell populations modulate behavior related to addiction is unknown. We demonstrate that PT neurons regulate the positive features of a drug experience whereas IT neurons regulate the negative features. These findings support a revised theory of cortical function in addiction, with distinct cells and circuits mediating reward and aversion.


Assuntos
Preparações Farmacêuticas , Células Piramidais/efeitos dos fármacos , Células Piramidais/fisiologia , Recompensa , Animais , Córtex Cerebral/fisiologia , Cocaína , Fenômenos Eletrofisiológicos , Masculino , Tratos Piramidais/fisiologia , Ratos , Ratos Sprague-Dawley
8.
Am J Emerg Med ; 40: 103-105, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33360606

RESUMO

BACKGROUND: Illicitly manufactured fentanyl and fentanyl analogues (IMFs) are being increasingly suspected in overdose deaths. However, few prior outbreaks have been reported thus far of patients with laboratory-confirmed IMF toxicity after reporting intent to use only nonopioid substances. Herein we report a case series of nine patients without opioid use disorder who presented to two urban emergency departments (EDs) with opioid toxicity after insufflating a substance they believed to be cocaine. CASE REPORTS: Over a period of under three hours, nine patients from five discrete locations were brought to two affiliated urban academic EDs. All patients denied prior illicit opioid use. All patients endorsed insufflating cocaine shortly prior to ED presentation. Soon after exposure, all developed lightheadedness and/or respiratory depression. Seven patients received naloxone en route to the hospital; all had improvement in respiratory function by arrival to the ED. None of the patients required any additional naloxone administration in the ED. All nine patients were discharged home after observation. Blood +/- urine samples were obtained from eight patients. All patients who provided specimens tested positive for cocaine metabolites and had quantifiable IMF concentrations, as well as several detectable fentanyl derivatives, analogues, and synthetic opioid manufacturing intermediates. DISCUSSION: IMF-contamination of illicit drugs remains a public health concern that does not appear to be restricted to heroin. This confirmed outbreak demonstrates that providers should elevate their level of suspicion for concomitant unintentional IMF exposure even in cases of non-opioid drug intoxication. Responsive public health apparatuses must prepare for future IMF-contamination outbreaks.


Assuntos
Cocaína/envenenamento , Overdose de Drogas/epidemiologia , Overdose de Drogas/terapia , Fentanila/envenenamento , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/terapia , Adulto , Serviço Hospitalar de Emergência , Feminino , Humanos , Drogas Ilícitas/envenenamento , Laboratórios , Masculino , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Cidade de Nova Iorque/epidemiologia
9.
Rev. Pesqui. (Univ. Fed. Estado Rio J., Online) ; 13: 41-49, jan.-dez. 2021. graf, tab
Artigo em Inglês, Português | LILACS, BDENF - Enfermagem | ID: biblio-1146053

RESUMO

Objetivo: Caracterizar o perfil dos adolescentes usuários de crack em tratamento no CAPS ADIII de Pelotas/ Rio Grande do Sul. Método: estudo descritivo de abordagem quantitativa realizado com 14 adolescentes usuários de crack em tratamento no CAPS ADIII. A coleta de dados ocorreu por meio de entrevistas utilizando o instrumento Teen Addiction Severity Index. Na análise dos dados empregou-se a estatística descritiva através de frequência simples. Resultados: a maioria é do sexo masculino, entre 13 e 17 anos, solteiros, negros. O início do uso de drogas variou de oito e 17 anos. Apresentam ensino fundamental incompleto e abandono escolar. Identificou-se o uso de cocaína/crack e a relação com atividades ilegais. Constatou-se a existência de conflitos familiares. O uso de substancias também é identificado entre os amigos próximos. Conclusão: os resultados apontam para a necessidade de investimentos em ações de promoção à saúde e prevenção ao uso de substâncias


Objective: To characterize the profile of adolescent user of crack in treatment in the CAPS ADIII in Pelotas/Rio Grande do Sul. Method: a descriptive study with a quantitative approach performed with 14 teenage users of crack treatment in the CAPS ADIII. The data collection occurred through interviews using the Teen Addiction Severity Index. In the data analysis was employed descriptive statistics through simple frequency. Results: the majority are male, between 13 and 17 years old, single, black. The onset of drug use ranged from eight to 17 years. They present incomplete elementary education and drop out of school. It was identified the use of cocaine/crack and the relation with illegal activities. The existence of family conflicts was verified. Substance use is also identified among close friends. Conclusion: the results point to the need for investments in actions to promote health and prevent substance use


Objetivo: Caracterizar el perfil del adolescente usuario de crack en tratamiento en el CAPS ADIII de Pelotas/Rio Grande do Sul. Método: estudio descriptivo de abordaje cuantitativo realizado con 14 adolescentes usuarios de crack en tratamiento en el CAPS ADIII. La recolección de datos ocurrió a través de entrevistas utilizando el instrumento Teen Addiction Severity Index. En el análisis de los datos se empleó la estadística descriptiva a través de frecuencia simple. Resultados: la mayoría es del sexo masculino, entre 13 y 17 años, solteros, negros. El inicio del uso de drogas varía de ocho a 17 años. Se presenta una enseñanza fundamental incompleta y abandono escolar. Se identificó el uso de cocaína/crack y la relación con actividades ilegales. Se constató la existencia de conflictos familiares. El uso de sustancias también se identifica entre los amigos cercanos. Conclusión: los resultados apuntan a la necesidad de inversiones en acciones de promoción a la salud y prevención del uso de sustancias


Assuntos
Humanos , Masculino , Feminino , Adolescente , Cocaína Crack , Grupo com Ancestrais do Continente Africano , Promoção da Saúde , Serviços de Saúde Mental , Evasão Escolar , Cocaína , Saúde do Adolescente , Prevenção de Doenças , Conflito Familiar , Usuários de Drogas
11.
Neuropsychopharmacology ; 46(2): 271-272, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873901
12.
J Anal Toxicol ; 44(8): 864-870, 2020 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-33313886

RESUMO

The objective of this study is to evaluate in vitro stability of cocaine compounds, cocaine (COC), benzoylecgonine (BE), ecgonine methyl ester (EME) and benzoylecgonine ethyl ester (EBE), in blood and urine, during post-analysis custody. Stability was evaluated by measuring percent recovery. Parameters evaluated were time of custody (1 year), storage temperature (-20°C and 4°C), influence of preservative (only for blood samples) and pH (only for urine samples). The impact of the temperature is very important in blood samples. At -20°C all compounds demonstrated to be stable, with recoveries higher than 80% after 1 year. In contrast, degradation was observed in the concentration for all four compounds when the samples were maintained at 4°C. In these same conditions, the influence of the preservative was also noticeable and a higher stability was found in samples preserved with NaF. COC and EBE had similar profiles, and both compounds disappeared after 30 days in samples without NaF and after 150 days in samples with NaF added. EME disappeared after 185 days and after 215 days in samples without and with preservative, respectively. BE recoveries, after 365 days of storage, were 68.5% (in samples with NaF) and 3.7% (in samples without NaF). In urine samples, the four compounds were stable in all the studied conditions except when samples were at pH 8 and stored at 4°C where the compounds disappeared (COC and EBE after 75 days of storage and EME after 15 days). The exception was BE, with a recovery of 23% after 1 year of storage. Of the temperatures evaluated, -20°C seems to be optimal for storage to maintain the stability of cocaine and metabolites in biological samples. This can be further enhanced by maintaining a pH of 4 in urine samples and adding a NaF preservative to blood.


Assuntos
Líquidos Corporais/metabolismo , Cocaína/metabolismo , Entorpecentes/metabolismo , Cromatografia Líquida de Alta Pressão , Cocaína/análogos & derivados , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Manejo de Espécimes , Temperatura
13.
J Anal Toxicol ; 44(8): 851-860, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33313888

RESUMO

Spectroscopic techniques combined with chemometrics are a promising tool for analysis of seized drug powders. In this study, the performance of three spectroscopic techniques [Mid-InfraRed (MIR), Raman and Near-InfraRed (NIR)] was compared. In total, 364 seized powders were analyzed and consisted of 276 cocaine powders (with concentrations ranging from 4 to 99 w%) and 88 powders without cocaine. A classification model (using Support Vector Machines [SVM] discriminant analysis) and a quantification model (using SVM regression) were constructed with each spectral dataset in order to discriminate cocaine powders from other powders and quantify cocaine in powders classified as cocaine positive. The performances of the models were compared with gas chromatography coupled with mass spectrometry (GC-MS) and gas chromatography with flame-ionization detection (GC-FID). Different evaluation criteria were used: number of false negatives (FNs), number of false positives (FPs), accuracy, root mean square error of cross-validation (RMSECV) and determination coefficients (R2). Ten colored powders were excluded from the classification data set due to fluorescence background observed in Raman spectra. For the classification, the best accuracy (99.7%) was obtained with MIR spectra. With Raman and NIR spectra, the accuracy was 99.5% and 98.9%, respectively. For the quantification, the best results were obtained with NIR spectra. The cocaine content was determined with a RMSECV of 3.79% and a R2 of 0.97. The performance of MIR and Raman to predict cocaine concentrations was lower than NIR, with RMSECV of 6.76% and 6.79%, respectively and both with a R2 of 0.90. The three spectroscopic techniques can be applied for both classification and quantification of cocaine, but some differences in performance were detected. The best classification was obtained with MIR spectra. For quantification, however, the RMSECV of MIR and Raman was twice as high in comparison with NIR. Spectroscopic techniques combined with chemometrics can reduce the workload for confirmation analysis (e.g., chromatography based) and therefore save time and resources.


Assuntos
Cocaína/análise , Cromatografia Gasosa-Espectrometria de Massas , Pós/análise , Análise Espectral
16.
Acute Med ; 19(3): 154-158, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33020760

RESUMO

A case report on a 36-year-old male patient presenting to the emergency department (ED) with chest tightness, nasal sounding voice and subcutaneous emphysema 72 hours after the nasal insufflation of approximately 0.5g of cocaine. A plain radiograph of the chest demonstrated an extensive pneumomediastinum with subcutaneous emphysema extending into his neck. A computerised tomography (CT) scan confirmed the above findings, along with a pneumorrhachis of the thoracic spine. He was admitted locally for further investigation and observation. Cocaine is the second most used illicit drug in the UK. The associated complications of cocaine can vary from acute coronary syndrome to acute psychosis. Pulmonological trauma secondary to cocaine misuse is commonly associated with inhalation of cocaine; we present this rare case of subcutaneous emphysema, pneumomediastinum and pneumorrhachis secondary to nasal insufflation. It is believed that deep nasal insufflation of cocaine is followed by forceful Valsalva manoeuvre, which allows for the rapid absorption of the drug and increases the euphoric effect. This forceful inhalation can lead to barotrauma and leakage of air into the posterior mediastinum.


Assuntos
Cocaína , Insuflação , Enfisema Mediastínico , Pneumorraque , Enfisema Subcutâneo , Adulto , Humanos , Insuflação/efeitos adversos , Masculino , Enfisema Mediastínico/induzido quimicamente , Enfisema Mediastínico/diagnóstico por imagem , Pneumorraque/diagnóstico por imagem , Pneumorraque/etiologia , Enfisema Subcutâneo/induzido quimicamente , Enfisema Subcutâneo/diagnóstico por imagem
17.
J Chromatogr A ; 1633: 461629, 2020 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-33128968

RESUMO

In this paper, a low-cost, rapid, easy, and potentially portable tool for the identification of cocaine and its semi-quantitative determination in oral fluid has been proposed. A field collection device has been designed, based on a cotton pad with an indicator and a molecularly imprinted polymer (MIP) sorbent, to selective retain cocaine from oral fluid components. After sample collection, cocaine is transferred by using phosphate buffer to the MIP and then eluted with 2-propanol. The obtained extract is analysed by ion mobility spectrometry (IMS), providing a cut-off value of 20 µg L-1 that identifies 100 % true-positive and 95 % true-negative samples. The MIP-IMS procedure has been validated by the analysis of oral fluid samples, collected from cocaine users at recreation environments, by comparing the results with lateral flow immunoassay and chromatographic reference methods. Thus, the proposed methodology allows a simple and fast cocaine identification that can be carried out in field by non-specialized personnel, such as health personnel, law enforcement bodies, and customs staff.


Assuntos
Cocaína/análise , Impressão Molecular , Saliva/química , Detecção do Abuso de Substâncias/instrumentação , Detecção do Abuso de Substâncias/métodos , Humanos , Espectrometria de Mobilidade Iônica , Polímeros/química
18.
J Anesth Hist ; 6(3): 172-173, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32921493

RESUMO

Joseph Burnett manufactured the diethyl ether used for William T.G. Morton's public demonstration of inhaled surgical anesthesia on October 16, 1846 (Ether Day). A later Burnett product was a hairdressing oil claimed to prevent baldness and dandruff. It contained cocoa-nut oil and was called Cocoaine. In 1902 and 1903, it was sometimes advertised as Burnett's Cocaine (rather than Cocoaine), possibly to emulate the economic success of coca-based beverages such as Vin Mariani and Coca-Cola. Coca leaves are now decocainized before use in preparation of Coca-Cola, and the recovered cocaine is used for scientific and dwindling medical purposes.


Assuntos
Cocaína/história , Caspa/história , Preparações para Cabelo/história , Publicidade/história , Alopecia/história , Alopecia/terapia , Anestésicos Inalatórios/história , Cacau , Caspa/terapia , Éter/história , Preparações para Cabelo/química , História do Século XIX , Humanos
19.
Clin Nucl Med ; 45(11): 919-920, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32969905

RESUMO

F-FDG is the most widely used PET tracer worldwide. Before the examination, recommendations are given to patients to avoid muscular activities, with the goal to limit F-FDG uptake in muscles. Here, we report the case of a 36-year-old man with Hodgkin disease referred to our department to perform an F-FDG PET/CT for immunotherapy assessment. The PET images showed a homogeneous, symmetric, and very intense uptake of the masticatory muscles. The medical examination exhibited a trismus, and the patient revealed to have been using cocaine 15 minutes before injection of F-FDG.


Assuntos
Cocaína/farmacologia , Fluordesoxiglucose F18/metabolismo , Músculos da Mastigação/metabolismo , Adulto , Artefatos , Transporte Biológico/efeitos dos fármacos , Doença de Hodgkin/diagnóstico por imagem , Doença de Hodgkin/metabolismo , Humanos , Masculino , Músculos da Mastigação/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
20.
Nat Commun ; 11(1): 4448, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895370

RESUMO

Substance abuse disorders are linked to alteration of circadian rhythms, although the molecular and neuronal pathways implicated have not been fully elucidated. Addictive drugs, such as cocaine, induce a rapid increase of dopamine levels in the brain. Here, we show that acute administration of cocaine triggers reprogramming in circadian gene expression in the striatum, an area involved in psychomotor and rewarding effects of drugs. This process involves the activation of peroxisome protein activator receptor gamma (PPARγ), a nuclear receptor involved in inflammatory responses. PPARγ reprogramming is altered in mice with cell-specific ablation of the dopamine D2 receptor (D2R) in the striatal medium spiny neurons (MSNs) (iMSN-D2RKO). Administration of a specific PPARγ agonist in iMSN-D2RKO mice elicits substantial rescue of cocaine-dependent control of circadian genes. These findings have potential implications for development of strategies to treat substance abuse disorders.


Assuntos
Relógios Circadianos/efeitos dos fármacos , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Cocaína/efeitos adversos , Núcleo Accumbens/efeitos dos fármacos , PPAR gama/metabolismo , Receptores de Dopamina D2/metabolismo , Administração Oral , Animais , Relógios Circadianos/fisiologia , Cocaína/administração & dosagem , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Dopamina/metabolismo , Injeções Intraperitoneais , Locomoção/fisiologia , Masculino , Camundongos , Camundongos Knockout , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Núcleo Accumbens/fisiopatologia , PPAR gama/agonistas , Pioglitazona/administração & dosagem , Receptores de Dopamina D2/genética , Recompensa , Transdução de Sinais
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