RESUMO
Many studies suggest a protective role of phenolic compounds in mood disorders. We aimed to assess the effect of Euterpe oleracea (açaí) seed extract (ASE) on anxiety induced by periodic maternal separation (PMS) in adult male rats. Animals were divided into 6 groups: control, ASE, fluoxetine (FLU), PMS, PMS+ASE, and PMS+FLU. For PMS, pups were separated daily from the dam for 3 h between postnatal day (PN) 2 and PN21. ASE (200 mg·kg-1·day-1) and FLU (10 mg·kg-1·day-1) were administered by gavage for 34 days after stress induction, starting at PN76. At PN106 and PN108, the rats were submitted to open field (OF) and forced swim tests, respectively. At PN110, the rats were sacrificed by decapitation. ASE increased time spent in the center area in the OF test, glucocorticoid receptors in the hypothalamus, tropomyosin receptor kinase B (TRKB) levels in the hippocampus, and nitrite levels and antioxidant activity in the brain stem (PMS+ASE group compared with PMS group). ASE also reduced plasma corticotropin-releasing hormone levels, adrenal norepinephrine levels, and oxidative damage in the brain stem in adult male offspring submitted to PMS. In conclusion, ASE treatment has an anti-anxiety effect in rats submitted to PMS by reducing hypothalamic-pituitary-adrenal axis reactivity and increasing the nitric oxide (NO)-brain-derived neurotrophic factor (BDNF)-TRKB pathway and antioxidant defense in the central nervous system. Novelty ASE has anti-anxiety and antioxidant effects in early-life stress. ASE reduces hypothalamic-pituitary-adrenal axis reactivity. The anxiolytic effect of ASE may involve activation of the NO-BDNF-TRKB pathway in the central nervous system.
Assuntos
Ansiolíticos/farmacologia , Antioxidantes/farmacologia , Privação Materna , Extratos Vegetais/farmacologia , Animais , Fator Neurotrófico Derivado do Encéfalo , Euterpe/química , Sistema Hipotálamo-Hipofisário , Masculino , Óxido Nítrico , Estresse Oxidativo , Sistema Hipófise-Suprarrenal , Ratos , Ratos Wistar , Receptor trkB , Sementes/química , Estresse PsicológicoRESUMO
Methylphenidate (MPD) is one of the most prescribed drugs for alleviating the symptoms of Attention Deficit/Hyperactivity Disorder (ADHD). However, changes in the molecular mechanisms related to MPD withdrawal and susceptibility to consumption of other psychostimulants in normal individuals or individuals with ADHD phenotype are not completely understood. The aims of the present study were: (i) to characterize the molecular differences in the prefrontal dopaminergic system of SHR and Wistar strains, (ii) to establish the neurochemical consequences of short- (24 hours) and long-term (10 days) MPD withdrawal after a subchronic treatment (30 days) with Ritalin® (Methylphenidate Hydrochloride; 2.5 mg/kg orally), (iii) to investigate the dopaminergic synaptic functionality after a cocaine challenge in adult MPD-withdrawn SHR and Wistar rats. Our results indicate that SHR rats present reduced [3H]-Dopamine uptake and cAMP accumulation in the prefrontal cortex (PFC) and are not responsive to dopaminergic stimuli in when compared to Wistar rats. After a 24-hour withdrawal of MPD, SHR did not present any alterations in [3H]-Dopamine Uptake, [3H]-SCH 23390 binding and cAMP production; nonetheless, after a 10-day MPD withdrawal, the results showed a significant increase of [3H]-Dopamine uptake, of the quantity of [3H]-SCH 23390 binding sites and of cAMP levels in these animals. Finally, SHR that underwent a 10-day MPD withdrawal and were challenged with cocaine (10 mg/kg i.p.) presented reduced [3H]-Dopamine uptake and increased cAMP production. Wistar rats were affected by the 10-day withdrawal of MPD in [3H]-dopamine uptake but not in cAMP accumulation; in addition, cocaine was unable to induce significant modifications in [3H]-dopamine uptake and in cAMP levels after the 10-day withdrawal of MPD. These results indicate a mechanism that could explain the high comorbidity between ADHD adolescent patients under methylphenidate treatment and substance abuse in adult life.
Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Cocaína/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Dopamina/metabolismo , Metilfenidato/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Animais , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Transporte Biológico , AMP Cíclico/metabolismo , Modelos Animais de Doenças , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Masculino , Ratos , Ratos Endogâmicos SHR , Receptores de Dopamina D1/metabolismoRESUMO
The most frequently used animal models of early weaning (EW) in rodents, maternal deprivation and pharmacological inhibition of lactation, present confounding factors, such as high stress or drug side effects, that can mask or interact with the effects of milk deprivation per se. Given these limitations, the development of new models of EW may provide useful information regarding the impact of a shortened period of breastfeeding on the endocrine and nervous systems, both during development and at adulthood. Using a model of EW in which lactating Wistar rat dams are wrapped with a bandage to block access to milk during the last three days of lactation, we have recently shown that the adult offspring presented higher body mass, hyperphagia, hyperleptinemia, leptin as well as insulin resistance, and higher adrenal catecholamine content at adulthood. Here, we used this EW model, which involves no pharmacological treatment or maternal separation, to analyze anxiety-like, novelty-seeking and memory/learning behavioral traits in the adult male offspring. To that end, animals were tested in the elevated plus maze, in the hole board arena and in the radial arm water maze. Except for an increased number of rearing events (a measure of vertical activity), no other behavioral differences were observed between EW and control animals. The contrasting behavioral results between the three EW models may be associated with differences in HPA axis function in the offspring at weaning, since it has been observed that bandaging does not affect corticosteronemia while maternal separation and pharmacological EW increase it.
Assuntos
Ansiedade/psicologia , Comportamento Exploratório , Aprendizagem em Labirinto , Memória , Desmame , Animais , Masculino , Modelos Animais , RatosRESUMO
OBJECTIVE: We have recently shown that maternal flaxseed supplementation during lactation induces insulin resistance in adult offspring. Here, we studied the effects of maternal dietary flaxseed during lactation on adipocyte morphology and leptin signaling in the hypothalamic-pituitary-thyroid axis as well as on behavioral traits in the adult progeny. METHODS: Lactating rats were fed a control (C) diet or a diet with 25% flaxseed (F). After weaning, pups received a standard diet until postnatal day (PN) 180. Male offspring were killed at PN21 and 180. Data were considered significant at P < 0.05. RESULTS: Weaned F rats presented a lower total and subcutaneous fat mass and higher subcutaneous adipocyte area (+48%), but at adulthood they presented higher subcutaneous and visceral adipocyte areas (+40% and 1.9-fold increase, respectively), with no change in body fat mass. At PN21, F pups had hyperleptinemia (+69%), lower T(3) (-33%), higher TSH (2.1-fold increase), higher pituitary leptin receptor (Ob-R, +11%), signal transducer and activator of transcription 3 (STAT3, +21%), and phosphorylated-STAT3 (p-STAT3, +77%) protein content. Adult F offspring only showed lower T(4) (-28%) and higher thyroid Ob-R (+52%) expression. Maternal flaxseed intake during lactation did not result in behavioral changes in the adult offspring. CONCLUSIONS: Maternal flaxseed supplementation decreases offspring adiposity and increases pituitary leptin signaling at weaning, but it induces hypertrophic adipocytes and higher thyroid leptin receptor in adulthood. The present data suggest that extensive use of flaxseed during lactation is undesirable.