6 resultados para FLUOXETINE TREATMENT
em Biblioteca Digital da Produção Intelectual da Universidade de São Paulo
Resumo:
In Ostariophysan fish, the detection of the alarm substance liberated into the water as a consequence of an attack by a predator elicits an alarm reaction or anti-predatory behavior. In this study, experiments were performed to: (i) describe and quantitatively characterize the behavioral and ventilatory responses in piaucu fish (Leporinus macrocephalus), individually and as part of a school, to conspecific alarm substance (CAS) and; (ii) test the effect of acute fluoxetine treatment on alarm reaction. Histological analysis revealed the presence of club cells in the intermediate and superficial layers of the epidermis. The predominant behavioral response to CAS was freezing for fish held individually, characterized by the cessation of the swimming activity as the animal settles to a bottom corner of the aquarium. Fish exposed to CAS showed decrease in the mean ventilatory frequency (approximately 13%) relative to control. In schools, CAS elicited a biphasic response that was characterized by erratic movements followed by increased school cohesion and immobility, reflected as an increased school cohesion (65.5% vs. -5.8% for controls) and in the number of animals near the bottom of the aquarium (42.0% vs. 6.5% for controls). Animals treated with single i.p. injections of fluoxetine (10 mu g/g b.w.) did not exhibit alarm behavior following CAS stimulation. These results show that an alarm pheromone system is present in piaucu fish, evidenced by the presence of epidermal club cells and an alarm reaction induced by CAS and consequently of a chemosensory system to transmit the appropriate information to neural structures responsible for initiating anti-predator behavioral responses. In addition, fluoxetine treatment caused an anxiolytic-like effect following CAS exposure. Thus, the alarm reaction in piaucu can be a useful model for neuroethological and pharmacological studies of anxiety-related states. (C) 2011 Elsevier Inc. All rights reserved.
Resumo:
The antidepressant fluoxetine has been under discussion because of its potential influence on cancer risk. It was found to inhibit the development of carcinogen-induced preneoplastic lesions in colon tissue, but the mechanisms of action are not well understood. Therefore, we investigated anti-proliferative effects, and used HT29 colon tumor cells in vitro, as well as C57BL/6 mice exposed to intra-rectal treatment with the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) as models. Fluoxetine increased the percentage of HT29 cells in the G(0)/G(1) phase of cell-cycle, and the expression of p27 protein. This was not related to an induction of apoptosis, reactive oxygen species or DNA damage. In vivo, fluoxetine reduced the development of MNNG-induced dysplasia and vascularization-related dysplasia in colon tissue, which was analyzed by histopathological techniques. An anti-proliferative potential of fluoxetine was observed in epithelial and stromal areas. It was accompanied by a reduction of VEGF expression and of the number of cells with angiogenic potential, such as CD133, CD34, and CD31-positive cell clusters. Taken together, our findings suggest that fluoxetine treatment targets steps of early colon carcinogenesis. This confirms its protective potential, explaining at least partially the lower colon cancer risk under antidepressant therapy.
Resumo:
Recent evidence indicates that the administration of inhibitors of neuronal nitric oxide synthase (nNOS) induces antidepressant-like effects in animal models such as the forced swimming test (FST). However, the neural circuits involved in these effects are not yet known. Therefore, this study investigated the expression of Fos protein, a marker of neuronal activity, in the brain of rats submitted to FST and treated with the preferential nNOS inhibitor, 7-nitroindazole (7-NI), or with classical antidepressant drugs (Venlafaxine and Fluoxetine). Male Wistar rats were submitted to a forced swimming pretest (PT) and, immediately after, started receiving a sequence of three ip injections (0, 5, and 23 h after PT) of Fluoxetine (10 mg/kg), Venlafaxine (10 mg/kg), 7-NI (30 mg/kg) or respective vehicles. One hour after the last drug injection the animals were submitted to the test session, when immobility time was recorded. After the FST they were sacrificed and had their brains removed and processed for Fos immunohistochemistry. Independent group of non-stressed animals received the same drug treatments, or no treatment (naive). 7-NI, Venlafaxine or Fluoxetine reduced immobility time in the FST, an antidepressant-like effect. None of the treatments induce significant changes in Fos expression per se. However, swimming stress induced significant increases in Fos expression in the following brain regions: medial prefrontal cortex, nucleus accumbens, locus coeruleus, raphe nuclei, striatum, hypothalamic nucleus, periaqueductal grey, amygdala, habenula, paraventricular nucleus of hypothalamus, and bed nucleus of stria terminalis. This effect was attenuated by 7-NI, Venlafaxine or Fluoxetine. These results show that 7-NI produces similar behavioral and neuronal activation effects to those of typical antidepressants, suggesting that these drugs share common neurobiological substrates.
Resumo:
Serotonin reuptake inhibitors and cognitive-behavior therapy (CBT) are considered first-line treatments for obsessive-compulsive disorder (OCD). However, little is known about their modulatory effects on regional brain morphology in OCD patients. We sought to document structural brain abnormalities in treatment-naive OCD patients and to determine the effects of pharmacological and cognitive-behavioral treatments on regional brain volumes. Treatment-naive patients with OCD (n = 38) underwent structural magnetic resonance imaging scan before and after a 12-week randomized clinical trial with either fluoxetine or group CBT. Matched-healthy controls (n = 36) were also scanned at baseline. Voxel-based morphometry was used to compare regional gray matter (GM) volumes of regions of interest (ROIs) placed in the orbitofrontal, anterior cingulate and temporolimbic cortices, striatum, and thalamus. Treatment-naive OCD patients presented smaller GM volume in the left putamen, bilateral medial orbitofrontal, and left anterior cingulate cortices than did controls (p<0.05, corrected for multiple comparisons). After treatment with either fluoxetine or CBT (n = 26), GM volume abnormalities in the left putamen were no longer detectable relative to controls. ROI-based within-group comparisons revealed that GM volume in the left putamen significantly increased (p<0.012) in fluoxetine-treated patients (n = 13), whereas no significant GM volume changes were observed in CBT-treated patients (n = 13). This study supports the involvement of orbitofronto/cingulo-striatal loops in the pathophysiology of OCD and suggests that fluoxetine and CBT may have distinct neurobiological mechanisms of action. Neuropsychopharmacology (2012) 37, 734-745; doi: 10.1038/npp.2011.250; published online 26 October 2011
Resumo:
Objective: To identify neuropsychological predictors of treatment response to cognitive-behavioral therapy (CBT) and fluoxetine in treatment-naive adults with obsessive-compulsive disorder (OCD). Method: Thirty-eight adult outpatients with OCD underwent neuropsychological assessment, including tasks of intellectual function, executive functioning and visual and verbal memory, before randomization to a 12-week clinical trial of either CBT or fluoxetine. Neuropsychological measures were used to identify predictors of treatment response in OCD. Results: Neuropsychological measures that predicted a better treatment response to either CBT or fluoxetine were higher verbal IQ (Wechsler Abbreviated Scale of Intelligence) (p = 0.008); higher verbal memory on the California Verbal Learning Test (p = 0.710); shorter time to complete part D (Dots) (p<0.001), longer time to complete part W (Words) (p = 0.025) and less errors on part C (Colors) (p<0.001) in the Victoria Stroop Test (VST). Fewer perseverations on the California Verbal Learning Test, a measure of mental flexibility, predicted better response to CBT, but worse response to fluoxetine (p = 0.002). Conclusion: In general, OCD patients with better cognitive and executive abilities at baseline were more prone to respond to either CBT or fluoxetine. Our finding that neuropsychological measures of mental flexibility predicted response to treatment in opposite directions for CBT and fluoxetine suggests that OCD patients with different neuropsychological profiles may respond preferentially to one type of treatment versus the other. Further studies with larger samples of OCD patients are necessary to investigate the heuristic value of such findings in a clinical context. (C) 2012 Elsevier Inc. All rights reserved.
Resumo:
Fluoxetine (FLX) is commonly used to treat anxiety and depressive disorders in pregnant women. Since FLX crosses the placenta and is excreted in milk, maternal treatment with this antidepressant may expose the fetus and neonate to increased levels of serotonin (5-HT). Long-term behavioral abnormalities have been reported in rodents exposed to higher levels of 5-HT during neurodevelopment. In this study we evaluated if maternal exposure to FLX during pregnancy and lactation would result in behavioral and/or stress response disruption in adolescent and adult rats. Our results indicate that exposure to FLX influenced restraint stress-induced Fos expression in the amygdala in a gender and age-specific manner. In male animals, a decreased expression was observed in the basolateral amygdala at adolescence and adulthood; whereas at adulthood, a decrease was also observed in the medial amygdala. A lack of FLX exposure effect was observed in females and also in the paraventricular nucleus of both genders. Regarding the behavioral evaluation, FLX exposure did not induce anhedonia in the sucrose preference test but decreased the latency to feed of both male and female adolescent rats evaluated in the novelty-suppressed feeding test. In conclusion, FLX exposure during pregnancy and lactation decreases acute amygdalar stress response to a psychological stressor in males (adolescents and adults) as well as influences the behavior of adolescents (males and females) in a model that evaluates anxiety and/or depressive-like behavior. Even though FLX seems to be a developmental neurotoxicant, the translation of these findings to human safe assessment remains to be determined since it is recognized that not treating a pregnant or lactating woman may also impact negatively the development of the descendants.