Evaluation of Depressive and Anxious Behavior with the Use of Propranolol in Melanoma-Bearing Mice

HIGHLIGHTS: Tumor progression and anxiety and depression behaviors under evaluation during propranolol use in murine melanoma. Evaluation of anxiety and depression through forced swimming behavior tests, elevated plus maze, open field and marble-burying test.

Abstract Melanoma, a severe form of skin cancer, has rapid growth and has been prone to behavioral disorders that worsen the patient's prognosis and survival. Among these psychic disorders can occur anxiety and depression, in addition to cognitive deficit. In order to try to elucidate the neuropsychological disorders that occur in melanoma, the objective of this study was to evaluate propranolol in tumor progression and in anxious and depressive behaviors in an animal model with melanoma. B16F10 cells were injected into C57BL6/J mice subsequently treated with propranolol at doses of 1.43 mg/kg and 5.71 mg/kg and evaluated for tumor growth and in open field, forced swimming, elevated plus maze and marble-burying test at initial time and consolidated tumor. As a result, the group treated with propranolol at a dose of 5.71 mg/kg showed less tumor growth. In the initial behavioral tests, melanoma altered the animals' motility, but anxious behavior was not detected. Depressive behavior was detected in the forced swimming test in the two doses of the treatment used. When taking time with consolidated tumor, there was a reduction in the locomotor activity of the animals in the open field test, impairing the analysis of anxious and depressive behavior. The data suggest that there was a reduction in the progression of melanoma, there was no anxious behavior in the animals, only the depressive behavior and the use of propranolol did not improve the evaluated behavior.

Effects of Hypericum perforatum on turning behavior in an animal model of Parkinson's disease

Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by the slow and progressive death of dopaminergic neurons in the (substantia nigra pars compact). Hypericum perforatum (H. perforatum) is a plant widely used as an antidepressant, that also presents antioxidant and anti-inflammatory properties. We evaluated the effects of H. perforatum on the turning behavior of rats submitted to a unilateral administration of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle as an animal model of PD. The animals were treated with H. perforatum (100, 200, or 400 mg/kg, v.o.) for 35 consecutive days (from the 28th day before surgery to the 7th day after). The turning behavior was evaluated at 7, 14 and 21 days after the surgery, and the turnings were counted as contralateral or ipsilateral to the lesion side. All tested doses significantly reduced the number of contralateral turns in all days of evaluation, suggesting a neuroprotective effect. However, they were not able to prevent the 6-OHDA-induced decrease of tyrosine hydroxylase expression in the lesioned striatum. We propose that H. perforatum may counteract the overexpression of dopamine receptors on the lesioned striatum as a possible mechanism for this effect. The present findings provide new evidence that H. perforatum may represent a promising therapeutic tool for PD.

A Doença de Parkinson é uma doença neurodegenerativa relacionada à idade, caracterizada pela morte lenta e progressiva de neurônios dopaminérgicos da substância negra pars compacta. O Hypericum perforatum (H. perforatum) é um fitoterápico utilizado como antidepressivo, apresentando propriedades antioxidantes, anti-inflamatórias e nootrópicas. Neste trabalho, avaliaram-se os efeitos do tratamento com H. perforatum no comportamento rotatório de ratos no modelo da doença de Parkinson induzido pela administração unilateral de 6-OHDA no feixe prosencefálico medial. Ratos Wistar machos foram tratados com H. perforatum (100, 200 ou 400 mg/kg, v.o.) por 35 dias (do 28º dia antes até o 7º dia após a lesão). As rotações ipsilaterais e contralaterais à lesão foram registradas no 7º, 14º e 21º dias após a cirurgia. As três doses de H. perforatum utilizadas reduziram o número de rotações contralaterais, indicando um possível efeito neuroprotetor da planta. Porém, o H. perforatum não impediu a redução na expressão da enzima tirosina hidroxilase no estriado lesionado, quantificada por Western blot. Propomos que o H. perforatum possa bloquear o aumento da expressão dos receptores dopaminérgicos no estriado lesionado com 6-OHDA. Entretanto, estudos adicionais são necessários para identificar o mecanismo exato pelo qual o H. perforatum reduziu o número de rotações contralaterais. Os resultados do presente estudo sugerem o H. perforatum como um potencial agente terapêutico para a doença de Parkinson.