RESUMO
Abscisic acid (ABA), a crucial phytohormone, is distributed in the brains of mammals and has been shown to have antidepressant effects in the chronic unpredictable mild stress test. The forced swim test (FST) is another animal model that can be used to assess antidepressant-like behavior in rodents. Here, we report that the antidepressant effects of ABA are associated with sensitivities to the FST in mice. Based on mean immobility in the 5-min forced swim pre-test, ICR mice were divided into short immobility mice (SIM) and long immobility mice (LIM) substrains. FST was carried out 8 days after drug administration. Learned helplessness, as shown by increased immobility, was only observed in SIM substrain and could be prevented by an 8-day ABA treatment. Our results show that ABA has antidepressant effects in SIM substrain and suggest that mice with learned helplessness might be more suitable for screening potential antidepressant drugs.
Assuntos
Ácido Abscísico/farmacologia , Antidepressivos/farmacologia , Transtorno Depressivo/diagnóstico , Transtorno Depressivo/tratamento farmacológico , Avaliação Pré-Clínica de Medicamentos/métodos , Testes Neuropsicológicos , Animais , Peso Corporal , Transtorno Depressivo/metabolismo , Modelos Animais de Doenças , Predisposição Genética para Doença , Desamparo Aprendido , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Camundongos Endogâmicos ICR , Atividade Motora/efeitos dos fármacos , RNA Mensageiro/metabolismo , Distribuição Aleatória , Natação , Sinapsinas/metabolismoRESUMO
The purpose of this study was to investigate the depression-like behavior performances of subclinical hypothyroidism (SCH) rat. SCH rat model was induced by hemi-thyroid electrocauterization, and the behavior performances were measured by sucrose preference test, force swimming test (FST), and tail suspension test (TST). SCH rat model was established successfully by hemi-thyroid electrocauterization. In the behavior tasks, SCH rats displayed depression-like behavior were indicated as a significant elevation of immobility time in both the TST and FST, though the sucrose preference was not significantly decreased. The index of left adrenal cortex in both SCH and clinical hypothyroidism (CH) group significantly increased, and many large lipid vacuoles were observed in the zona fasciculata cells. The serum corticosterone concentration and hypothalamic corticotropin-releasing hormone mRNA expression 2 h after behavior test was markedly up-regulated in CH rats, but not SCH rats, indicated that SCH induced a less impairment of HPA axis than CH did. The important finding of this study was that the concentration of hippocampal T3 was lower in SCH group than that of the sham group. Furthermore, the results of Pearson correlation test showed that the immobility behaviors in TST and FST were both negatively correlated with hippocampal T3 concentration. Taking together, our results indicated that SCH could result in depression-like behavior, accompanied with subtle hyperactivity of HPA axis. The reduced hippocampal T3 prior to the reduction of thyroid hormone in serum might be taken as an early sign of hippocampus impairment in the progression from SCH to CH.
Assuntos
Comportamento Animal/fisiologia , Depressão/etiologia , Sistema Hipotálamo-Hipofisário/metabolismo , Hipotireoidismo/complicações , Sistema Hipófise-Suprarrenal/metabolismo , Hormônios Tireóideos/sangue , Córtex Suprarrenal/patologia , Animais , Corticosterona/sangue , Depressão/metabolismo , Depressão/fisiopatologia , Modelos Animais de Doenças , Eletrocoagulação/métodos , Hipocampo/metabolismo , Hipotireoidismo/etiologia , Hipotireoidismo/metabolismo , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Glândula Tireoide/patologia , Tri-Iodotironina/sangue , Tri-Iodotironina/metabolismoRESUMO
BACKGROUND: Corticotrophin-releasing hormone (CRH) is considered to be the central driving force of the hypothalamic-pituitary-adrenal axis, which plays a key role in the stress response and depression. Clinical reports have suggested that excess retinoic acid (RA) is associated with depression. Abscisic acid (ABA) and RA are direct derivatives of carotenoids and share a similar molecular structure. Here, we proposed that ABA also plays a role in the regulation of CRH activity sharing with the RA signaling pathway. METHODS: [3H]-ABA radioimmunoassay demonstrated that the hypothalamus of rats shows the highest concentration of ABA compared with the cortex and the hippocampus under basal conditions. RESULTS: Under acute stress, ABA concentrations increased in the serum, but decreased in the hypothalamus and were accompanied by increased corticosterone in the serum and c-fos expression in the hypothalamus. Moreover, chronic ABA administration increased sucrose intake and decreased the mRNA expression of CRH and retinoic acid receptor alpha (RARα) in the hypothalamus of rats. Furthermore, ABA improved the symptom of chronic unpredictable mild stress in model rats, as indicated by increased sucrose intake, increased swimming in the forced swim test, and reduced mRNA expression of CRH and RARα in the rat hypothalamus. In vitro, CRH expression decreased after ABA treatment across different neural cells. In BE(2)-C cells, ABA inhibited a series of retinoid receptor expression, including RARα, a receptor that could facilitate CRH expression directly. CONCLUSIONS: These results suggest that ABA may play a role in the pathogenesis of depression by downregulating CRH mRNA expression shared with the RA signaling pathway.
