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1.
BMC Pediatr ; 24(1): 487, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39080575

RESUMEN

Some patients with autism and severe intellectual disability may experience uncontrolled aggression, causing serious injury or harm to others, and the therapeutic ineffectiveness of traditional pharmacological and behavioral treatment may aggravate symptoms. Deep brain stimulation (DBS) has been tested in patients with little evidence in children and adolescents. Therefore, we analyzed the efficacy and safety of DBS in refractory aggression in pediatric subjects with autism (ASD) and severe intelligence deficit (ID).Methods A meta-analytic review of Web of Science (WOS) and Scopus articles, following Prisma criteria. A total of 555 articles were identified, but after applying the inclusion criteria, only 18 were analyzed. The review of the registries and the extraction of information was performed by 2 independent groups, to reduce the evaluator's bias. For the description of the results, pediatric patients with ASD or ID present in each registry, with an application of specialized scales (Overt aggression scale, OAS, and THE modified version of the OAS, MOAS) pre and post-DBS, with a clinical follow-up of at least 12 months, were considered valid. Clinical improvement was calculated using tests of aggressiveness. In each registry with available data and then pooling the means of all patients in the OAS and MOAS, the effect size of DBS (overall and per study) was estimated. Finally, the adapted NOS scale was applied to rate the studies' quality and level of bias.Results In the studies analyzed, 65/100 were pediatric patients, with a mean age of 16.8 years. Most of the studies were conducted in South America and Europe. In all teams, aggressive behavior was intractable, but only 9 groups (53/65) applied specialized scales to measure aggressiveness, and of these, only 51 subjects had a follow-up of at least 12 months. Thus, in 48/51 a clinical improvement of patients was estimated (94.2%), with a considerable overall effect size (OAS: d = 4.32; MOAS: d = 1.46). However, adverse effects and complications were found in 13/65 subjects undergoing DBS. The brain target with the most evidence and the fewest side effects was the posteromedial hypothalamic nuclei (pHypN). Finally, applying the adapted NOS scale, quality, and bias, only 9 studies show the best indicators.Conclusion An optimal level of efficacy was found in only half of the publications. This is mainly due to design errors and irrelevant information in the reports. We believe that DBS in intractable aggressiveness in children and adolescents with ASD and severe ID can be safe and effective if working groups apply rigorous criteria for patient selection, interdisciplinary assessments, objective scales for aggressiveness, and known surgical targets.


Asunto(s)
Agresión , Estimulación Encefálica Profunda , Discapacidad Intelectual , Humanos , Estimulación Encefálica Profunda/métodos , Niño , Discapacidad Intelectual/terapia , Adolescente , Trastorno Autístico/terapia , Resultado del Tratamiento
2.
Rev Colomb Psiquiatr ; 2023 Apr 14.
Artículo en Español | MEDLINE | ID: mdl-37360790

RESUMEN

Introduction: The coronavirus pandemic continues to affect the mental health of healthcare personnel in Latin America (LA). Objective: To estimate the prevalence of psychological disturbances and associated risk factors for mental health in healthcare personnel in LA during the second year of the COVID-19 pandemic. Method: This multicenter cross-sectional study included a total sample of 5437 healthcare professionals from Argentina, Bolivia, Chile, Colombia, Ecuador, and Peru. The PHQ-9, GAD-7, and a brief demographic questionnaire were used. The prevalence of anxiety and depression was estimated based on the cut-off points of the instruments. Two multivariate logistic regressions were performed. Results: A population burden of anxiety (40.1%) and depression (62.2%) was found in healthcare personnel in LA. Among professionals in Argentina (OR = 1.374; P<.001), those working in state hospitals (OR = 1.536; P<.003), frontline healthcare workers for COVID patients (OR = 1.848; P<.001), general practitioners (OR = 1.335; P<.001), and specialists (OR = 1.298; P<.001), a higher risk of experiencing mental disorders was observed. Among women, younger personnel, and administrative staff, a higher probability of experiencing anxiety and depression was identified. Conclusions: The burden of mental disorders on healthcare personnel in Latin America is alarming. Psychological support services are necessary, aimed at providing measures for professionals to develop healthy coping mechanisms that mitigate the impact of the pandemic on their well-being and facilitate post-crisis adjustment.

3.
Rev Colomb Psiquiatr ; 2022 Sep 06.
Artículo en Español | MEDLINE | ID: mdl-36092252

RESUMEN

Background and objectives: An increase in emotional disturbances and complaints about cognitive performance has been observed in Latin American healthcare workers during the SARS-CoV-2 pandemic, which can affect attention capacity and increase the levels of stress and burnout of these professionals. The objective was to analyse subjective cognitive complaints (SCC) and associated factors in health personnel during the COVID-19 pandemic in five Latin American countries.Methods: Multicentre cross-sectional study, which included 3,738 professionals from Colombia, Chile, Argentina, Ecuador, Bolivia, and Peru. The Generalized Anxiety Disorder Scale (GAD-7) and the Patient Health Questionnaire (PHQ-9) was used to assess depression, and the Mini-Z to assess Burnout. For the SCC, an item on cognitive concerns in attention and memory was used.Results: The prevalence of cognitive complaints was 69.2%. The factors associated with a higher risk of SCC were the scores in the GAD-7, PHQ and Mini-Z, in addition to being part of the Ecuadorian health personnel.Conclusions: There is a high prevalence of SCC in health personnel, which is modulated by emotional states and stress.

4.
Innov Clin Neurosci ; 19(4-6): 48-50, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35958969

RESUMEN

Introduction: Recent reports have shown several cases of cerebrovascular events after vaccination against COVID-19. The effects have been described mainly in women within the first two weeks of receiving the vaccine. Clinical Case: We describe here the first Colombian case of a cerebrovascular event after vaccination against COVID-19 in a 67-year-old woman with a vascular history. Four days after application of the messenger ribonucleic acid (mRNA) vaccine, she exhibited deviation of the labial commissure, ipsilateral ptosis, and limitation of march with lateralization. The event was associated with a subacute ischemic event in the right thalamus in parasagittal situation, changes in chronic ischemic microangiopathy of small vessels, and vascular crossing in the right cerebellar angle, without other alternative causes. Conclusion: The development and rapid use of vaccines has allowed the hospitalization and mortality statistics associated with COVID-19 to be reduced, but at the same time, it has generated concern about the potential side effects, generating controversy among the general population, especially in individuals with cardiovascular diseases. In our case, we provided evidence for the discussion of potential cerebrovascular events related to the application of vaccines in older people with a history of cerebrovascular diseases. This was done in order to analyze and control in subsequent studies the modulation of medical history on the likely effects of vaccination. However, despite the unavoidable side effects, the benefits of vaccination are superior.

5.
J Transl Med ; 19(1): 494, 2021 12 04.
Artículo en Inglés | MEDLINE | ID: mdl-34863209

RESUMEN

The maintained attention is the cause of great functional limitations in CFS/ME, a disease that mainly affects women in the central period of life. Cognitive function is explored using the Montreal Cognitive Assessment, the maintained attention using the Toulouse-Piéron test with which the Global Index of Attention and Perception (GIAP) is obtained, the fatigue using the visual analog scale and the perception of effort using the modified Borg scale. The final sample were 84 patients (66 women/18 men) who met diagnostic criteria (Fukuda-1994, Carruthers-2011) and 22 healthy controls (14 women/8 men). Most of patients maintain normal cognitive function, showing low or very low attention score in the 70% of patients with a marked cognitive fatigue compared to the control group (p < 0.05). There were no significant differences between genders in GIAP or fatigue for CFS/ME; however, sick women perceive cognitive effort higher than men. Deficits in sustained attention and the perception of fatigue, so effort after performing the proposed test are a sensitive and reliable indicator that allows us to substantiate a clinical suspicion and refer patients for further studies in order to confirm or rule out CFS/ME.


Asunto(s)
Síndrome de Fatiga Crónica , Biomarcadores , Cognición , Síndrome de Fatiga Crónica/diagnóstico , Femenino , Humanos , Masculino
6.
Front Psychiatry ; 12: 735784, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34707521

RESUMEN

The aim of present paper is to identify clinical phenotypes in a cohort of patients affected of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Ninety-one patients and 22 healthy controls were studied with the following questionnaires, in addition to medical history: visual analogical scale for fatigue and pain, DePaul questionnaire (post-exertional malaise, immune, neuroendocrine), Pittsburgh sleep quality index, COMPASS-31 (dysautonomia), Montreal cognitive assessment, Toulouse-Piéron test (attention), Hospital Anxiety and Depression test and Karnofsky scale. Co-morbidities and drugs-intake were also recorded. A hierarchical clustering with clinical results was performed. Final study group was made up of 84 patients, mean age 44.41 ± 9.37 years (66 female/18 male) and 22 controls, mean age 45 ± 13.15 years (14 female/8 male). Patients meet diagnostic criteria of Fukuda-1994 and Carruthers-2011. Clustering analysis identify five phenotypes. Two groups without fibromyalgia were differentiated by various levels of anxiety and depression (13 and 20 patients). The other three groups present fibromyalgia plus a patient without it, but with high scores in pain scale, they were segregated by prevalence of dysautonomia (17), neuroendocrine (15), and immunological affectation (19). Regarding gender, women showed higher scores than men in cognition, pain level and depressive syndrome. Mathematical tools are a suitable approach to objectify some elusive features in order to understand the syndrome. Clustering unveils phenotypes combining fibromyalgia with varying degrees of dysautonomia, neuroendocrine or immune features and absence of fibromyalgia with high or low levels of anxiety-depression. There is no a specific phenotype for women or men.

7.
Artículo en Inglés | MEDLINE | ID: mdl-32598313

RESUMEN

Background In previous studies, we have observed that glutamate antagonists injected within the nucleus accumbens septi (NAS) induced an anxiolytic-like effect in the elevated plus maze (EPM) test in rats. In the present study, the effect of Atenolol, a specific Beta Adreno-receptor antagonist in the EPM was studied in male rats bilaterally cannulated NAS. Methods Rats were divided into five groups that received either 1 µL injections of saline or atenolol in different doses (0.75, 1 or 2 µg/1 µL, n=15-16) 15 min before testing. Results Time Spent in the Open Arm was modified by treatment (F=4.563, p=0.006, df 3). This was increased by the lowest dose of atenolol (p<0.05), by the medium doses (p<0.001) and also by the highest dose (p<0.01). Time per Entry was modified by treatment (F=4.54, p=0.06, df 3). This parameter was increased by the lowest dose of atenolol (p<0.01), but not for the medium and higher doses. Conclusions We conclude that Atenolol beta receptor blockade in the accumbens lead to an anxiolytic-like effect related to an increase in the time spent in the open arm and in the time per entry, showing specific behavioral patterns.


Asunto(s)
Antagonistas de Receptores Adrenérgicos beta 1/farmacología , Ansiolíticos/farmacología , Atenolol/farmacología , Núcleo Accumbens/metabolismo , Antagonistas de Receptores Adrenérgicos beta 1/administración & dosificación , Animales , Ansiolíticos/administración & dosificación , Atenolol/administración & dosificación , Conducta Animal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Prueba de Laberinto Elevado , Masculino , Ratas , Factores de Tiempo
8.
Hippocampus ; 30(9): 938-957, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32285544

RESUMEN

The importance of the hippocampus in spatial learning is well established, but the precise relative contributions by the dorsal (septal) and ventral (temporal) subregions remain unresolved. One debate revolves around the extent to which the ventral hippocampus contributes to spatial navigation and learning. Here, separate small subtotal lesions of dorsal hippocampus or ventral hippocampus alone (destroying 18.9 and 28.5% of total hippocampal volume, respectively) spared reference memory acquisition in the water maze. By contrast, combining the two subtotal lesions significantly reduced the rate of acquisition across days. This constitutes evidence for synergistic integration between dorsal and ventral hippocampus in mice. Evidence that ventral hippocampus contributes to spatial/navigation learning also emerged early on during the retention probe test as search preference was reduced in mice with ventral lesions alone or combined lesions. The small ventral lesions also led to anxiolysis in the elevated plus maze and over-generalization of the conditioned freezing response to a neutral context. Similar effects of comparable magnitudes were seen in mice with combined lesions, suggesting that they were largely due to the small ventral damage. By contrast, small dorsal lesions were uniquely associated with a severe spatial working memory deficit in the water maze. Taken together, both dorsal and ventral poles of the hippocampus contribute to efficient spatial navigation in mice: While the integrity of dorsal hippocampus is necessary for spatial working memory, the acquisition and retrieval of spatial reference memory are modulated by the ventral hippocampus. Although the impairments following ventral damage (alone or in combination with dorsal damage) were less substantial, a wider spectrum of spatial learning, including context conditioning, was implicated. Our results encourage the search for integrative mechanism between dorsal and ventral hippocampus in spatial learning. Candidate neural substrates may include dorsoventral longitudinal connections and reciprocal modulation via overlapping polysynaptic networks beyond hippocampus.


Asunto(s)
Agonistas de Aminoácidos Excitadores/toxicidad , Hipocampo/fisiología , Trastornos de la Memoria/inducido químicamente , Memoria a Corto Plazo/fisiología , Recuerdo Mental/fisiología , Memoria Espacial/fisiología , Animales , Hipocampo/efectos de los fármacos , Hipocampo/patología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Trastornos de la Memoria/patología , Trastornos de la Memoria/fisiopatología , Memoria a Corto Plazo/efectos de los fármacos , Recuerdo Mental/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Memoria Espacial/efectos de los fármacos , Técnicas Estereotáxicas
9.
J Basic Clin Physiol Pharmacol ; 29(3): 241-246, 2018 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-29902911

RESUMEN

BACKGROUND: In previous studies, we have observed that specific N-methyl-d-aspartic acid (NMDA) antagonists and non-NMDA antagonists injected within the nucleus accumbens septi (NAS) induced an anxiolytic-like effect in the plus maze test in rats. In the present study, the effect of intracanalicular blockade of NMDA receptors using dizocilpine in the plus maze was studied in male rats bilaterally cannulated NAS. METHODS: Rats were divided into five groups that received either 1 µL injections of saline or dizocilpine (MK-801, [5R,10S]-[+]-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine) in different doses (0.5, 1, 2, or 4 µg) 15 min before testing. RESULTS: Time spent in the open arm increased under dizocilpine treatment with the two higher doses (2 and 4 µg, p<0.05), extreme arrivals were increased by the three higher doses (1 µg, p<0.05; 2 and 4 µg, p<0.01), and open arm entries by the three higher doses (1, 2, and 4 µg, p<0.05). A dose-effect relationship was observed in all cases. CONCLUSIONS: We conclude that dizocilpine-glutamatergic blockade in the accumbens lead to an anxiolytic-like effect and a behavioral disinhibition related to an increase in some motoric parameters, showing specific behavioral patterns.


Asunto(s)
Maleato de Dizocilpina/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Aprendizaje por Laberinto/efectos de los fármacos , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Animales , Ansiolíticos/administración & dosificación , Ansiolíticos/farmacología , Conducta Animal/efectos de los fármacos , Maleato de Dizocilpina/administración & dosificación , Relación Dosis-Respuesta a Droga , Antagonistas de Aminoácidos Excitadores/administración & dosificación , Masculino , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/metabolismo , Ratas , Ratas Sprague-Dawley , Factores de Tiempo
10.
Behav Brain Res ; 339: 286-296, 2018 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-29102592

RESUMEN

The water maze is one of the most widely employed spatial learning paradigms in the cognitive profiling of genetically modified mice. Oftentimes, tests of reference memory (RM) and working memory (WM) in the water maze are sequentially evaluated in the same animals. However, critical difference in the rules governing efficient escape from the water between WM and RM tests is expected to promote the adoption of incompatible mnemonic or navigational strategies. Hence, performance in a given test is likely poorer if it follows the other test instead of being conducted first. Yet, the presence of such negative transfer effects (or proactive interference) between WM and RM training in the water maze is often overlooked in the literature. To gauge whether this constitutes a serious concern, the present study determined empirically the magnitude, persistence, and directionality of the transfer effect in wild-type C57BL/6 mice. We contrasted the order of tests between two cohorts of mice. Performance between the two cohorts in the WM and RM tests were then separately compared. We showed that prior training of either test significantly reduced performance in the subsequent one. The statistical effect sizes in both directions were moderate to large. Although extended training could overcome the deficit, it could re-emerge later albeit in a more transient fashion. Whenever RM and WM water maze tests are conducted sequentially in the same animals - regardless of the test order, extra caution is necessary when interpreting the outcomes in the second test. Counterbalancing test orders between animals is recommended.


Asunto(s)
Atención/fisiología , Aprendizaje por Laberinto/fisiología , Memoria a Corto Plazo/fisiología , Conducta Espacial/fisiología , Animales , Conducta Animal , Masculino , Ratones Endogámicos C57BL , Transferencia de Experiencia en Psicología/fisiología
11.
Acta Pol Pharm ; 71(2): 323-7, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25272653

RESUMEN

Depression in menopausal women has been widely described for many years ago and is related to hormonal decrease, mainly estrogens. The use of soy has been proposed as a possible coadjutant alternative to treat menopausal depressive disorder. In the present pilot clinical trial the effect of soybean, antidepressants and the association of soybean with antidepressants was studied in 40 depressive menopausal women for three months. Patients were divided in four groups of 10 women: fluoxetine (10 mg), soybean (100 mg), sertraline (50 mg), and sertraline (50 mg) plus soybean (100 mg). The Hamilton and Zung Depression Scales were used to measure the treatment effects. Values at the beginning and at the end of the study were compared. In all cases a significant difference was observed when the treated groups were compared vs. their untreated situation in both scales (p < 0.001). When a comparison between pre- minus post-treatment Zung scale scores was done, the effect induced by the association of sertraline and soybean was significantly higher than the other groups (p < 0.05). These effects were also seen using the Hamilton scale scores, showing significant differences between the association vs. soybean (p < 0.05) and setraline (p < 0.05) groups, but not vs. fluoxetine group. We conclude that soybean has an antidepressant effect per se, and the association of soybean and antidepressants increases their effects.


Asunto(s)
Antidepresivos/uso terapéutico , Trastorno Depresivo/tratamiento farmacológico , Glycine max/química , Posmenopausia/efectos de los fármacos , Antidepresivos/administración & dosificación , Trastorno Depresivo/etiología , Quimioterapia Combinada , Femenino , Fluoxetina/administración & dosificación , Fluoxetina/uso terapéutico , Humanos , Persona de Mediana Edad , Proyectos Piloto , Posmenopausia/psicología , Estudios Prospectivos , Sertralina/administración & dosificación , Sertralina/uso terapéutico , Seno Sagital Superior , Resultado del Tratamiento
12.
Biomed Res Int ; 2014: 183248, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25003108

RESUMEN

Central nucleus of the amygdala (CeA) is one of the most important regulatory centres for the emotional processes. Among the different neurotransmitter systems present in this nucleus, AT1 receptors have been also found, but their role in the generation and modulation of emotions is not fully understood. The present work evaluated the effect of intra-amygdalar injection of losartan (AT1 receptor antagonist) and angiotensin II (Ang II) in the anxiety state induced by fear-potentiated plus maze in male Wistar rats. Fear in the elevated plus maze can be potentiated by prior inescapable footshock stress. The decrease in the time spent in the open arms induced by the inescapable footshock was totally prevented by losartan (4 pmol) administration in CeA. It was also found that Ang II (48 fmol) administration decreased the time spent in the open arms in animals with or without previous footshock exposure. The locomotor activity and grooming behaviour were also evaluated. The results obtained from the different parameters analyzed allowed us to conclude that the Ang II AT1 receptors in CeA are involved in the anxiety state induced by stress in the fear-potentiated plus-maze behaviour.


Asunto(s)
Angiotensina II/farmacología , Núcleo Amigdalino Central/fisiología , Miedo/efectos de los fármacos , Receptor de Angiotensina Tipo 1/metabolismo , Animales , Conducta Animal/efectos de los fármacos , Núcleo Amigdalino Central/efectos de los fármacos , Aseo Animal/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Ratas Wistar , Factores de Tiempo
13.
Pharmacol Rep ; 65(3): 566-78, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23950579

RESUMEN

BACKGROUND: The effect of the agonism on γ-aminobutyric acid (GABA) receptors was studied within medial prefrontal cortex (mPFC), amygdala (AMY) and ventral hipocampus (VH) in the plus-maze test in male rats bilaterally cannulated. These structures send glutamatergic projections to the nucleus accumbens septi (NAS), in which interaction and integration between these afferent pathways has been described. In a previous study of our group, blockade of glutamatergic transmission within NAS induced an anxiolytic like effect. METHODS: Three rat groups received either saline or dipotassium chlorazepate (1 or 2 µg/1 µl solution) 15 min before testing. Time spent in the open arms (TSOA), time per entry (TPE), extreme arrivals (EA), open and closed arms entries (OAE, CAE) and relationship between open- and closed-arms quotient (OCAQ) were recorded. RESULTS: In the AMY injected group TSOA, OAE and EA were increased by the higher doses of dipotassium chlorazepate (p < 0.01). In the mPFC, TPE was decreased by both doses (p < 0.05). Injection within ventral hippocampus (VH) decreased TSOA, OAE and OCAQ with lower doses (p < 0.05). When the three studied saline groups were compared, TSOA, OAE, EA and OCAQ were enhanced in the VH group when compared to mPFC and AMY (p < 0.001). Insertion of inner canula (p < 0.001, p < 0.01, p < 0.01) and saline injection showed an increasing significant difference (p < 0.001 in all cases) with the action of guide cannula alone within VH in TSOA, OAE and EA. CONCLUSION: We conclude that the injection of dipotassium chlorazepate has a differential effect depending of the brain area, leading to facilitatory and inhibitory effects on anxiety processing.


Asunto(s)
Amígdala del Cerebelo/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Clorazepato Dipotásico/administración & dosificación , Fármacos actuantes sobre Aminoácidos Excitadores/administración & dosificación , Hipocampo/efectos de los fármacos , Núcleo Accumbens/efectos de los fármacos , Corteza Prefrontal/efectos de los fármacos , Animales , Ansiolíticos/administración & dosificación , Ansiedad/tratamiento farmacológico , Agonistas del GABA/administración & dosificación , Masculino , Ratas
14.
Behav Brain Res ; 242: 166-77, 2013 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-23276606

RESUMEN

Prepulse inhibition (PPI) of the acoustic startle reflex refers to the attenuation of the startle response to an intense pulse stimulus when it is shortly preceded by a weak non-startling prepulse stimulus. It is a well-established high-throughput translational measure of pre-attentive sensory gating, and its impairment is detected in several neuropsychiatric diseases including schizophrenia. It has been hypothesized that PPI might be associated with, or predictive of, cognitive deficiency in such diseases, and therefore provide an efficient assay for screening drugs with potential pro-cognitive efficacy. Free from any predetermined disease model, the present study evaluated in a homogeneous cohort of inbred C57BL/6 mice the presence of a statistical link between PPI expression and cognitive performance. Performance indices in a spatial reference memory test and a working memory test conducted in the Morris water maze, and contextual fear conditioning were correlated against pre-existing baseline PPI expression. A specific correlative link between working memory and PPI induced by weak (but not strong) prepulse was revealed. In addition, a correlation between habituation of the startle reflex and reference memory was identified for the first time: a stronger overt habituation effect was associated with superior spatial search accuracy. The PPI paradigm thus provides two independent predictors of dissociable cognitive traits in normal C57BL/6 mice; and they might serve as potential markers for high-throughput evaluation of potential cognitive enhancers, especially in the context of schizophrenia where deficits in startle habituation and PPI co-exist.


Asunto(s)
Habituación Psicofisiológica/fisiología , Memoria a Corto Plazo/fisiología , Inhibición Neural/fisiología , Reflejo de Sobresalto/fisiología , Retención en Psicología/fisiología , Percepción Espacial/fisiología , Estimulación Acústica , Análisis de Varianza , Animales , Reacción Cataléptica de Congelación/fisiología , Masculino , Aprendizaje por Laberinto , Ratones , Ratones Endogámicos C57BL , Valor Predictivo de las Pruebas , Psicoacústica , Tiempo de Reacción , Factores de Tiempo
15.
Psychopharmacology (Berl) ; 225(2): 341-52, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22899220

RESUMEN

RATIONALE: The startle reflex to a sudden intense acoustic pulse stimulus is attenuated if the pulse is shortly preceded by a weak prepulse stimulus. This represents a form of sensory gating, known as prepulse inhibition (PPI), observable across species. PPI is modulated by dopamine and readily disrupted by acute amphetamine. Prior repeated exposures to amphetamine also disrupt PPI even when the drug is not present during test, suggesting that a sensitized mesolimbic dopamine system-inducible even by a single exposure to amphetamine-might be responsible. However, this causative link has been challenged by inconsistent efficacy between different amphetamine pre-treatment regimes, which all robustly sensitize the behavioral response to amphetamine. METHODS: Here, the presence of such a link in reverse was tested by comparing the propensity to develop amphetamine sensitization between high- and low-PPI expressing individuals identified within a homogeneous cohort of C57BL/6 mice. Comparison of dopamine content including its metabolites was performed separately in drug naïve mice by post-mortem HPLC. RESULTS: Behavioral sensitization was substantially stronger in the low-PPI group compared with the high-PPI group, while the magnitude of their response to the first amphetamine challenge was similar. Dopamine content within the nucleus accumbens and medial prefrontal cortex was significantly higher in low-PPI relative to high-PPI mice. CONCLUSION: Individuals with weak sensory gating characterized by low basal PPI expression may be more susceptible to the development of dopamine sensitization and therefore at greater risk of developing schizophrenia. Conversely, high baseline expression might predict a resistance to dopaminergic sensitization.


Asunto(s)
Anfetamina/farmacología , Dopaminérgicos/farmacología , Dopamina/metabolismo , Reflejo de Sobresalto/efectos de los fármacos , Animales , Cromatografía Líquida de Alta Presión , Masculino , Ratones , Ratones Endogámicos C57BL , Núcleo Accumbens/metabolismo , Corteza Prefrontal/metabolismo , Filtrado Sensorial/efectos de los fármacos
16.
Pharmacol Rep ; 64(1): 54-63, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22580520

RESUMEN

It has been recognized that the stress-related peptides are involved in anxiety states. Angiotensin II receptor blockade by systemic administration of the AT(1) receptor antagonists has been proposed as a new treatment possibility for anxiety disorders. For better understanding of the related mechanisms, in this study we evaluated effects of bilateral intraamygdaloid injections of 2 (LOS 2) and 4 (LOS 4) µg of losartan (LOS), a selective AT(1) receptor antagonist, on the behavior of the not stressed and acutely stressed rats in an elevated "plus" maze. Under non-stress conditions, LOS 4 increased time spent in the open arms (p < 0.01), number of extreme open arm arrivals (p < 0.05), time per entry (p < 0.01), and the number of total arm entries (p < 0.05) showing thus considerable anxiolytic activity. The open arm extreme arrivals were increased by LOS 4 in both not stressed (p < 0.05) and stressed (p < 0.05) rats. When no stressed and stressed LOS 4 animals were compared, time per entry and the number of closed arm entries (p < 0.05, both) were decreased in the latter group. Moreover, the LOS 4 stressed rats had significantly increased open/closed arm quotient (p < 0.05) as compared to the both control and LOS 4 non-stress group (p < 0.05, both). These findings suggest that the AT(1) receptor blockade in amygdala is important for the anxiolytic action of LOS (and probably other AT(1) receptor blockers) under both non-stress and stress conditions.


Asunto(s)
Amígdala del Cerebelo/efectos de los fármacos , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Ansiolíticos/farmacología , Conducta Animal/efectos de los fármacos , Losartán/farmacología , Amígdala del Cerebelo/metabolismo , Animales , Ansiedad/tratamiento farmacológico , Ansiedad/metabolismo , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Ratas , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/metabolismo
17.
Behav Brain Res ; 230(1): 208-14, 2012 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-22342492

RESUMEN

Glycine transporter 1 (GlyT1) is a potential pharmacological target to ameliorate memory deficits attributable to N-methyl-d-aspartate receptor (NMDAR) hypofunction. Disruption of glycine-reuptake near excitatory synapses is expected to enhance NMDAR function by increasing glycine-B site occupancy. Genetic models with conditional GlyT1 deletion restricted to forebrain neurons have yielded several promising promnesic effects, yet its impact on working memory function remains essentially unanswered because the previous attempt had yielded un-interpretable outcomes. The present study clarified this important outstanding lacuna using a within-subject multi-test approach. Here, a consistent lack of effects was convincingly demonstrated across three working memory tests - the radial arm maze, the cheeseboard maze, and the water maze. These null outcomes contrasted with the phenotype of enhanced working memory performance seen in mutant mice with GlyT1 deletion extended to cortical/hippocampal glial cells. It follows that glial-based GlyT1 might be more closely linked to the modulation of working memory function, and raises the possibility that neuronal and glial GlyT1 may regulate cognitive functions via dissociable mechanisms.


Asunto(s)
Proteínas de Transporte de Glicina en la Membrana Plasmática/deficiencia , Memoria a Corto Plazo/fisiología , Neuronas/metabolismo , Prosencéfalo/citología , Análisis de Varianza , Animales , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/genética , Señales (Psicología) , Habituación Psicofisiológica/genética , Masculino , Aprendizaje por Laberinto/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Prosencéfalo/metabolismo , Factores de Tiempo
18.
Educ. méd. (Ed. impr.) ; 14(1): 27-34, mayo 2011. ilus, tab
Artículo en Español | IBECS | ID: ibc-92769

RESUMEN

Objetivo. Evaluar y comparar la percepción que del ambiente educativo tienen los estudiantes de medicina de dos universidades iberoamericanas: Universidad de Chile (UCH) y Universidad Nacional de Cuyo (UNC), que desarrollan un currículo tradicional y un currículo basado en problemas, respectivamente. Sujetos y métodos. Participaron 465 estudiantes: 232 de la UCH y 233 de la UNC. La distribución fue de 84 y 70 estudiantes para el primer curso, 77 y 97 para el tercero, y 71 y 66 para el quinto, respectivamente. Se aplicó el cuestionario DREEM, que consiste en 50 ítems, agrupados en cinco dimensiones: percepción de la enseñanza, percepción de los profesores, autopercepción académica, percepción de la atmósfera educativa y autopercepción social. Resultados. Las puntuaciones totales fueron mayores en los tres cursos de la UNC. Resultaron similares en todos los cursos de ambas universidades, excepto en el quinto curso de la UCH. Respecto a la percepción acerca de los profesores, los estudiantes de quinto curso de la UCH mostraron las puntuaciones más bajas, mientras que los estudiantes del primer curso de la UNC tuvieron la mejor percepción. Resultados similares se obtuvieron en la autopercepción académica. La percepción del ambiente de aprendizaje fue mejor en la UNC y la autopercepción social tuvo puntuaciones similares en todos los cursos de ambas universidades. Conclusiones. Las diferencias observadas entre ambas universidades podrían atribuirse a sus diferentes currículos. El currículo basado en problemas parece ser mejor valorado que el tradicional. Nuestro estudio corrobora la eficacia del cuestionario DREEM para identificar fortalezas y debilidades del currículo y para evaluar la calidad de la enseñanza en facultades de medicina (AU)


Aim. To assess and compare the perception about the educational environment of medical students from two Latin-American universities, University of Chile (UCH) and National University of Cuyo (UNC), which develop a traditional curriculum and a problem based curriculum, respectively. Subjects and methods. A transversal study was performed in 465 students: 232 from the UCH and 233 from the UNC. The distribution was 84/70 for the first course, 77/97 for the third one and 71/66 for the fifth one, respectively. The DREEM questionnaire, which consists of 50 items, was applied. It covers 5 dimensions of the educational environment: perception about learning, perception about teachers, academic self-perception, perception about educational climate and social self-perception. Results. Total DREEM scores were significantly higher in the UNC. Scores were similar in all courses from both universities, with the exception of fifth course UCH. Regarding their perception about teachers, students of the fifth course UCH showed the lowest score, whereas students of the first course UNC had the best perception. Similar results were obtained for the academic auto-perception; while the perception of the learning environment obtained higher scores in the three courses from the UNC. Social auto-perception was similar in all courses tested in this study. Conclusions. Differences observed between both universities could be attributed to their different curricula. Problem based curriculum seems to be better appreciated than the traditional one. Our study corroborates the efficacy of the DREEM questionnaire to identify strengths and weaknesses of the curriculum and for the assessment of teaching quality in medical schools (AU)


Asunto(s)
Humanos , Masculino , Femenino , Adulto , Evaluación Educacional/estadística & datos numéricos , Facultades de Medicina/estadística & datos numéricos , Estudiantes de Medicina/estadística & datos numéricos , Percepción Social , Satisfacción Personal , Aprendizaje Basado en Problemas/estadística & datos numéricos
19.
Neuroreport ; 22(2): 83-7, 2011 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-21164371

RESUMEN

The amygdaloid complex is involved in anxiety or fear responses to stressful stimuli. In this study the effect of neuropeptide-EI on anxiety-like behavior and its influence on adrenocortical function was tested in male Wistar rats that were injected bilaterally in the basolateral amygdala with neuropeptide-EI (1 µg/1 µl) or artificial cerebrospinal fluid and placed on the plus maze. The plasma corticosterone levels were analyzed in controls and plus-maze exposed animals. Neuropeptide-EI in the basolateral amygdala significantly decreased the time spent in open arms but had no effect on locomotor activity, showing an anxiogenic effect. However, neuropeptide administration did not change serum corticosterone levels compared with vehicle controls. Our results suggest that the anxiogenic effect of neuropeptide-EI could be independent of the hypothalamic-pituitary-adrenocortical system response.


Asunto(s)
Amígdala del Cerebelo/efectos de los fármacos , Ansiedad/inducido químicamente , Conducta Animal/efectos de los fármacos , Oligopéptidos/administración & dosificación , Animales , Ansiedad/sangre , Corticosterona/sangre , Masculino , Microinyecciones , Actividad Motora/efectos de los fármacos , Ratas , Ratas Wistar
20.
Behav Brain Res ; 136(1): 171-7, 2002 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-12385802

RESUMEN

Upon systemic administration of apomorphine, a potent dopamine agonist, pigeons show a bout of pecking behaviour. When the drug is repeatedly administered a sensitization takes place that is associated with pronounced discrimination learning. Here we show that intra-cerebral injections of apomorphine in the periphery of the nucleus accumbens of pigeons also elicit pecking. We additionally show that injections of 5-amino-phosphonohepatnoic acid, a NMDA-glutamate receptor blocker, into the Acc impairs the performance of a learned visual discrimination incorporating pecking as a choice response. We conclude that, as it is the case in mammals, the control mechanisms of learned sensory-motor behaviour in birds involves dopaminergic and glutamatergic synaptic transmission within the nucleus accumbens area.


Asunto(s)
Conducta Animal/efectos de los fármacos , Agonistas de Dopamina/farmacología , Dopamina/fisiología , Antagonistas de Aminoácidos Excitadores/farmacología , Ácido Glutámico/fisiología , Núcleo Accumbens/fisiología , Animales , Apomorfina/administración & dosificación , Apomorfina/farmacología , Columbidae , Aprendizaje Discriminativo/efectos de los fármacos , Maleato de Dizocilpina/administración & dosificación , Maleato de Dizocilpina/farmacología , Inyecciones , Núcleo Accumbens/anatomía & histología , Quinoxalinas/administración & dosificación , Quinoxalinas/farmacología , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Técnicas Estereotáxicas , Estimulación Química
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