RESUMO
Ivermectin is a human and veterinary antiparasitic drug which is one of the most widely used in the world. Studies from our group have revealed several behavioral and neurochemical impairments induced by therapeutic doses of ivermectin in adult rats. However, the effects on juveniles remain unknown. Ivermectin has been prescribed for juvenile humans, pets and farm animals, which still show remarkable development and postnatal maturation and may be more susceptible to drug interventions. Hence, we studied the behavioral and neurochemical effects of two therapeutical doses (0.2 and 1.0â¯mg/kg) of ivermectin in juvenile rats. As it is underestimated in prescriptions, the stress factor was also studied. Ivermectin 1.0â¯mg/kg induced hyperlocomotion in juvenile rats. Association of 1.0â¯mg/kg ivermectin with stress induced hypolocomotion in rats. Ivermectin 1.0â¯mg/kg whether or not associated with stress exacerbated socialization of rats. Ivermectin did not induce anxiety-like behavior neither affected corticosterone levels of juvenile rats. The motor/exploratory behavioral findings induced by association of ivermectin and stress seem to be triggered after the increase in the striatal serotonergic system activity. Association of ivermectin with stress increased striatal dopamine levels, which increased (excessive) social play behavior. Our results suggest a review of the prescribed dose of ivermectin for juvenile humans and pets. Moreover, the stress factor should be considered for ivermectin medical prescriptions, since it may exacerbate behavioral and neurochemical disturbances.
Assuntos
Antiparasitários/toxicidade , Ivermectina/toxicidade , Atividade Motora/efeitos dos fármacos , Comportamento Social , Animais , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/fisiologia , Masculino , Ratos , Ratos Wistar , Neurônios Serotoninérgicos/efeitos dos fármacos , Neurônios Serotoninérgicos/fisiologia , Estresse Fisiológico/efeitos dos fármacosRESUMO
OBJECTIVE: The present study evaluated the nociceptive response induced by dentin hypersensitivity after dental erosion in rats that were exhibited to unpredictable chronic mild stress (UCMS)-induced depressive-like behavior. DESIGN: Adult male rats were subjected to UCMS (depression [D] group) or not (no depression [ND] group) for 30days and received either acidic solution to induce dental erosion (E) or water (W), thus forming the WND, END, WD, and ED groups. After the end of treatment, depressive-like parameters (i.e., sucrose preference and immobility in the forced swim test) and dentin hypersensitivity were evaluated. Plasma tumor necrosis factor α (TNF-α) and corticosterone levels were measured, and astrocytic glial fibrillary acidic protein (GFAP) expression was evaluated in the prefrontal cortex, hippocampus, amygdala, and hypothalamus. RESULTS: Administration of the acidic solution potentiated dentin hypersensitivity and increased corticosterone levels in the ED group compared with the WD group. TNF-α levels only increased in the WD group. The ED group exhibited an increase in astrocytic GFAP expression in the hypothalamus and prefrontal cortex but decreases in the hippocampus. CONCLUSIONS: These results suggest that UCMS exacerbated the nociceptive response associated with dentin hypersensitivity, concomitant with an increase in plasma corticosterone levels. Hypothalamic and prefrontal cortex astrogliosis in the ED group may be attributable to the increase in corticosterone associated to UCMS procedure. The reduction of astrocytic GFAP expression in the hippocampus in the ED group supports the association between dentin hypersensitivity and depression.
Assuntos
Sensibilidade da Dentina/etiologia , Depressão/complicações , Estresse Fisiológico , Animais , Corticosterona/sangue , Depressão/metabolismo , Modelos Animais de Doenças , Proteína Glial Fibrilar Ácida/metabolismo , Técnicas Imunoenzimáticas , Masculino , Microscopia Eletrônica de Varredura , Ratos , Ratos Wistar , Propriedades de Superfície , Fator de Necrose Tumoral alfa/sangueRESUMO
Recent studies have demonstrated the intimate relationship between depression and immune disturbances. Aware of the efficacy limits of existing antidepressant drugs and the potential anti-inflammatory properties of propentofylline, we sought to evaluate the use of propentofylline as a depression treatment. We used a rat model of depression induced by repetitive lipopolysaccharide (LPS) administrations. We have studied sickness behavior, by assessing daily body weight, open field behavior, and TNF-α plasmatic levels. Anxiety-like behavior (light-dark test), depressive-like behavior (forced swim test), plasmatic levels of the brain-derived neurotrophic factor (BDNF, depression biomarker), and central glial fibrillary acidic protein (GFAP) expression (an astrocyte biomarker) were also evaluated. LPS induced body weight loss, open field behavior impairments (decreased locomotion and rearing, and increased immobility), and increased TNF-α levels in rats, compared with control group. Thus, LPS induced sickness behavior. LPS also increased the immobility and reduced climbing in the forced swim test, when compared with the control group, i.e., LPS induced depressive-like behavior in rats. Propentofylline prevented sickness behavior after four days of consecutive treatment, as well as prevented the depressive-like behavior after five days of consecutive treatments. Propentofylline also prevented the increase in GFAP expression induced by LPS. Neither LPS nor propentofylline has influenced the anxiety and BDNF levels of rats. In conclusion, repetitive LPS administrations induced sickness behavior and depressive-like behavior in rats. Propentofylline prevented both sickness behavior and depressive-like behavior via neuroinflammatory pathway. The present findings may contribute to a better understanding and treatment of depression and associated diseases.
Assuntos
Depressão/tratamento farmacológico , Lipopolissacarídeos/toxicidade , Xantinas/uso terapêutico , Animais , Antidepressivos , Ansiedade/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Transtorno Depressivo/tratamento farmacológico , Modelos Animais de Doenças , Proteína Glial Fibrilar Ácida/metabolismo , Comportamento de Doença/efeitos dos fármacos , Imuno-Histoquímica , Masculino , Fotomicrografia , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismoRESUMO
No Brasil, informações acerca da anaplasmose em pequenos ruminantes são escassas. Neste artigo, é apresentado um levantamento epidemiológico para Anaplasma sp., em ovinos provenientes de três micro-regiões (Sertão, Zona da Mata e Agreste) do estado de Alagoas, Nordeste do Brasil, por ELISA com MSP5 recombinante de Anaplasma marginale. A frequência de ovinos soropositivos foi de 8,92% (20/224). Entre as regiões, as frequências foram: Sertão 6,89% (2/29), Zona da Mata 10,46% (18/172) e Agreste 0% (0/23). Diferenças entre as ocorrências de ovinos soropositivos não foram estatisticamente significativas. No entanto, a baixa frequência detectada na região do Sertão e Agreste em relação à Zona da Mata possivelmente ocorreu devido à influência das condições climáticas sobre o desenvolvimento dos carrapatos vetores. Esses achados pontuais necessitam de futuros estudos para elucidar os aspectos epidemiológicos e econômicos da anaplasmose ovina na região.
In Brazil, information concerning anaplasmosis in small ruminants is scarce. In this paper, it is shown an epidemiological survey of Anaplasma sp. in sheep from three micro-regions (Sertão, Zona da Mata and Agreste) of Alagoas, Northeast of Brazil, by enzyme linked immunosorbent assay - ELISA with recombinant major surface protein - MSP5 of Anaplasma marginale. The frequency of seropositive sheep was 8.92% (20/224). Among regions, frequencies were: Sertão - 6.89% (2/29), Zona da Mata 10.46% (18/172), and Agreste 0% (0/23). Differences in the frequencies of seropositive sheep were not statistically significant. However, the lower frequencies were detected in the semi-arid micro-regions (Sertão and Agreste), possibly, due to the unsuitable climatic conditions for the development of tick vectors. These findings point to the need of further studies, to elucidate epidemiological and economic aspects of sheep anaplasmosis in the region.
RESUMO
No Brasil, informações acerca da anaplasmose em pequenos ruminantes são escassas. Neste artigo, é apresentado um levantamento epidemiológico para Anaplasma sp., em ovinos provenientes de três micro-regiões (Sertão, Zona da Mata e Agreste) do estado de Alagoas, Nordeste do Brasil, por ELISA com MSP5 recombinante de Anaplasma marginale. A frequência de ovinos soropositivos foi de 8,92% (20/224). Entre as regiões, as frequências foram: Sertão 6,89% (2/29), Zona da Mata 10,46% (18/172) e Agreste 0% (0/23). Diferenças entre as ocorrências de ovinos soropositivos não foram estatisticamente significativas. No entanto, a baixa frequência detectada na região do Sertão e Agreste em relação à Zona da Mata possivelmente ocorreu devido à influência das condições climáticas sobre o desenvolvimento dos carrapatos vetores. Esses achados pontuais necessitam de futuros estudos para elucidar os aspectos epidemiológicos e econômicos da anaplasmose ovina na região.
In Brazil, information concerning anaplasmosis in small ruminants is scarce. In this paper, it is shown an epidemiological survey of Anaplasma sp. in sheep from three micro-regions (Sertão, Zona da Mata and Agreste) of Alagoas, Northeast of Brazil, by enzyme linked immunosorbent assay - ELISA with recombinant major surface protein - MSP5 of Anaplasma marginale. The frequency of seropositive sheep was 8.92% (20/224). Among regions, frequencies were: Sertão - 6.89% (2/29), Zona da Mata 10.46% (18/172), and Agreste 0% (0/23). Differences in the frequencies of seropositive sheep were not statistically significant. However, the lower frequencies were detected in the semi-arid micro-regions (Sertão and Agreste), possibly, due to the unsuitable climatic conditions for the development of tick vectors. These findings point to the need of further studies, to elucidate epidemiological and economic aspects of sheep anaplasmosis in the region.