937 resultados para plus-maze
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Pós-graduação em Biociências - FCLAS
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Pós-graduação em Biociências - FCLAS
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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It has been demonstrated that, on abrupt withdrawal, patients with chronic exposure can experience a number of symptoms indicative of a dependent state. In clinical patients, the earliest to arise and most persistent signal of withdrawal from chronic benzodiazepine (Bzp) treatment is anxiety. In laboratory animals, anxiety-like effects following abrupt interruption of chronic Bzp treatment can also be reproduced. In fact, signs that oscillate from irritability to extreme fear behaviours and seizures have been described already. As anxiety remains one of the most important symptoms of Bzp withdrawal, in this study we evaluated the anxiety levels of rats withdrawn from diazepam. Also studied were the effects on the motor performance and preattentive sensory gating process of rats under diazepam chronic treatment and upon 48-h withdrawal on three animal models of anxiety, the elevated plus-maze (EPM), ultrasonic vocalizations (USV) and startle + prepulse inhibition tests. Data obtained showed an anxiolytic- and anxiogenic-like profile of the chronic intake of and withdrawal from diazepam regimen in the EPM test, 22-KHz USV and startle reflex. Diazepam chronic effects or its withdrawal were ineffective in promoting any alteration in the prepulse inhibition (PPI). However, an increase of PPI was achieved in both sucrose and diazepam pretreated rats on 48-h withdrawal, suggesting a procedural rather than a specific effect of withdrawal on sensory gating processes. It is also possible that the prepulse can function as a conditioned stimulus to informing the delivery of an aversive event, as the auditory startling-eliciting stimulus. All these findings are indicative of a sensitization of the neural substrates of aversion in diazepam withdrawn animals without concomitant changes on the processing of sensory information
A influência do ciclo estral no comportamento das linhagens de ratos congênica SLA16 e isogênica SHR
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Several studies use only male rats in their experiments, even with all the evidence of differences between the sexes, not only in the reproductive behavior but also in the development of diseases. This absence of studies using female rats is due in part to the estrous cycle. It is known that one estrous cycle lasts four to 5 days and consists of four phases: proestrus, estrus, metestrus and diestrus. Ramos et al. (1999) identified and mapped a QTL in an F2 population derived from interbreeding of strains of SHR (spontaneously hypertensive rats) and Lewis (LEW) rats and found, on chromosome 4, the first QTL of the world related to anxiety in rats. After several backcrosses between SHR and LEW strains, it was developed a congenic strain called SLA16, to refine the study of this QTL. This QTL corresponds to a large genomic region, approximately 75 million basepairs (Mb), and was first called Ofil1 (inner open field locomotion 1). Currently it is called Anxrr16 (anxiety-related response region 16) according to the rat genome database (RGD). Izidio et al. (2011) suggested that the natural fluctuation of the hormones in the estrous cycle of female rats could influence the effects of this locus on behavior. That is, females in DP (diestrus-proestrus) present the QTL in the same genomic region that males, while females in EM (estrus-metestrus) do not present it. The effects of the estrous cycle in the SLA16 strain and its isogenic control SHR were analyzed on the elevated plus maze (EPM), black and white box and on the open field test (OF). In the open field test, the SLA16 strain had higher central locomotion (F=5.0, p <0.05) and peripheral locomotion (F=12.6, p <0.01) compared to the SHR strain. In the elevated plus maze test, the SLA16 strain had the higher number of entries (F=9.5, p <0.01) and time spent in the open arms (F=10.3, p <0.01) compared to the SHR strain. Finally, in the black and white box test, the SLA16 lineage spent more time ...
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Introduction: Aortic insufficiency (AoI), a volume overload, is characterized by the diastolic reflux of blood from the regurgitating aorta to the left ventricle. This effect results from malfunctioning aortic cusps. The main cause of AoI in developing countries is rheumatic fever, including Brazil, and valvar degeneration in developed countries. There is a strong association between cardiovascular diseases and depression. Selective serotonin reuptake inhibitors (SSRI) are one of the most prescribed antidepressants in the world. Previous studies of our laboratory showed that the utilization of a SSRI, paroxetine, improved cardiac function in rats with sub-chronic AoI and reduced the daily ingestion of hypertonic sodium (NaCl 0,3M). Cardiovascular diseases can determine behavior changes like increase of anxiety, and it is yet unknown if AoI would determine anxiety or anhedonia, incapacity of obtaining pleasure through physical or sensorial experiences. A possible target for SSRI action could be a change in the expression of enzyme isoforms that collaborate in the contractile function of the heart muscle, like the heavy chains of myosine, the sarcoplasmatic reticulum Ca2+/ATPase (SERCA) and its regulator protein, phospholamban (PLB). Objectives: Evaluation of behavior parameters for anxiety and anhedonia state and genic expression of a-myosine, b-myosine, SERCA2a and PLB in the heart tissue of rats with subchronic AoI that received treatment with an SSRI (paroxetine) for 4 weeks. Methods: Surgery to induce AoI was performed on male Wistar rats, anxiety was evaluated by the elevated plus-maze (EPM) and state of anhedonia was tested by ingestion of 2% sucrose solution. After euthanasia the heart tissue was collected and total RNA was extracted to be analyzed by the RT-qPCR method. Results: Heart fractional shortening was preserved in rats with AoI that were treated compared to rats with AoI that were not treated. There was no statistically ...
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Atypical antipsychotics are also used in the treatment of anxiety-related disorders. Clinical and preclinical evidence regarding their intrinsic anxiolytic efficacy has been mixed. In this study, we examined the potential anxiolytic-like effects of risperidone and olanzapine, and compared them with haloperidol, chlordiazepoxide (a prototype of sedative–anxiolytic drug) or citalopram (a selective serotonin reuptake inhibitor). We used a composite of two-way avoidance conditioning and acoustic startle reflex model and examined the effects of drug treatments during the acquisition phase (Experiment 1) or extinction phase (Experiments 2 and 3) on multiple measures of conditioned and unconditioned fear/anxiety-like responses. In Experiment 4, we further compared risperidone, olanzapine, haloperidol, citalopram and chlordiazepoxide in a standard elevated plus maze test. Results revealed three distinct anxiolytic-like profiles associated with risperidone, olanzapine and chlordiazepoxide. Risperidone, especially at 1.0 mg/kg, significantly decreased the number of avoidance responses, 22 kHz ultrasonic vocalization, avoidance conditioning-induced hyperthermia and startle reactivity, but did not affect defecations or time spent on the open arms. Olanzapine (2.0 mg/kg, sc) significantly decreased the number of avoidance responses, 22 kHz vocalization and amount of defecations, but it did not inhibit startle reactivity and time spent on the open arms. Chlordiazepoxide (10 mg/kg, ip) significantly decreased the number of 22 kHz vocalization, avoidance conditioning-induced hyperthermia and amount of defecations, and increased time spent on the open arms, but did not decrease avoidance responses or startle reactivity. Haloperidol and citalopram did not display any anxiolytic-like property in these tests. The results highlight the importance of using multiple measures of fear-related responses to delineate behavioral profiles of psychotherapeutic drugs.
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Cohabitation for 14 days with Ehrlich tumor-bearing mice was shown to increase locomotor activity, to decrease hypothalamic noradrenaline (NA) levels, to increase NA turnover and to decrease innate immune responses and decrease the animals' resistance to tumor growth. Cage mates of a B16F10 melanoma-bearer mice were also reported to show neuroimmune changes. Chemosignals released by Ehrlich tumor-bearing mice have been reported to be relevant for the neutrophil activity changes induced by cohabitation. The present experiment was designed to further analyze the effects of odor cues on neuroimmune changes induced by cohabitation with a sick cage mate. Specifically, the relevance of chemosignals released by an Ehrlich tumor-bearing mouse was assessed on the following: behavior (open-field and plus maze); hypothalamic NA levels and turnover; adrenaline (A) and NA plasmatic levels; and host resistance induced by tumor growth. To comply with such objectives, devices specifically constructed to analyze the influence of chemosignals released from tumor-bearing mice were employed. The results show that deprivation of odor cues released by Ehrlich tumor-bearing mice reversed the behavioral, neurochemical and immune changes induced by cohabitation. Mice use scents for intraspecies communication in many social contexts. Tumors produce volatile organic compounds released into the atmosphere through breath, sweat, and urine. Our results strongly suggest that volatile compounds released by Ehrlich tumor-injected mice are perceived by their conspecifics, inducing the neuroimmune changes reported for cohabitation with a sick companion. (C) 2011 Elsevier Inc. All rights reserved.
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Cannabinoid receptor 1 (CB1) agonists usually induce dose-dependent biphasic effects on anxiety-related responses. Low doses induce anxiolytic-like effects, whereas high doses are ineffective or anxiogenic, probably due to activation of Transient Receptor Potential Vanilloid Type 1 (TRPV1) channels. In this study we have investigated this hypothesis by verifying the effects of the CB1/TRPV1 agonist ACEA injected into the prelimbic medial prefrontal cortex (PL) and the participation of endocannabinoids in the anxiolytic-like responses induced by TRPV1 antagonism, using the elevated plus-maze (EPM) and the Vogel conflict test (VCT). Moreover, we verified the expression of these receptors in the PL by double labeling immunofluorescence. ACEA induced anxiolytic-like effect in the intermediate dose, which was attenuated by previous injection of AM251, a CB1 receptor antagonist. The higher and ineffective ACEA dose caused anxiogenic- and anxiolytic-like effects, when injected after AM251 or the TRPV1 antagonist 6-iodonordihydrocapsaicin (6-I-CPS), respectively. Higher dose of 6-I-CPS induced anxiolytic-like effects both in the EPM and the VCT, which were prevented by previous administration of AM251. In addition, immunofluorescence showed that CB1 and TRPV1 receptors are closely located in the PL These results indicate that the endocannabinoid and endovanilloid systems interact in the PL to control anxiety-like behavior. (C) 2012 Elsevier Ltd. All rights reserved.
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Alcoholism is a chronic disorder characterized by the appearance of a withdrawal syndrome following the abrupt cessation of alcohol intake that includes symptoms of physical and emotional disturbances, anxiety being the most prevalent symptom. In humans, it was shown that anxiety may increase the probability of relapse. In laboratory animals, however, the use of anxiety to predict alcohol preference has remained difficult. Excitatory amino acids as glutamate have been implicated in alcohol hangover and may be responsible for the seizures and anxiety observed during withdrawal. The dorsal periaqueductal gray (DPAG) is a midbrain region critical for the modulation/expression of anxiety- and fear-related behaviors and the propagation of seizures induced by alcohol withdrawal, the glutamate neurotransmission being one of the most affected. The present study was designed to evaluate whether low- (LA) and high-anxiety rats (HA), tested during the alcohol hangover phase, in which anxiety is the most prevalent symptom, are more sensitive to the reinforcing effects of alcohol when tested in a voluntary alcohol drinking procedure. Additionally, we were interested in investigating the main effects of reducing the excitatory tonus of the dorsal midbrain, after the blockade of the ionotropic glutamate receptors into the DPAG, on the voluntary alcohol intake of HA and LA motivated rats that were made previously experienced with the free operant response of alcohol drinking. For this purpose, we used local infusions of the N-metil D-Aspartato (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-kainate receptors antagonist DL-2-Amino-7-phosphonoheptanoic acid - DL-AP7 (10 nmol/0.2 mu l) and L-glutamic acid diethyl ester - GDEE (160 nmol/0.2 mu l) respectively. Alcohol intoxication was produced by 10 daily bolus intraperitonial (IP) injections of alcohol (2.0 g/kg). Peak-blood alcohol levels were determined by gas-chromatography analysis in order to assess blood-alcohol content. Unconditioned and conditioned anxiety-like behavior was assessed by the use of the fear-potentiated startle procedure (FPS). Data collected showed that anxiety and alcohol drinking in HA animals are positively correlated in animals that were made previously familiarized with the anxiolytic effects of alcohol. In addition, anxiety-like behavior induced during alcohol hangover seems to be an effect of changes in glutamatergic neurotransmission into DPAG possibly involving AMPA/kainate and NMDA receptors, among others. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.