The effects of captopril on lipopolysaccharide-induced sickness behaviors in rats.

Neuro-immune mediators play an important role in the development of sickness behaviors. In the present study, the effect of captopril on sickness behaviors caused by lipopolysaccharide (LPS) was studied in the rats. The animals were randomized into the following groups: control, sham, 10 mg kg-1 captopril - LPS (Capto 10-LPS), 50 mg kg-1 captopril - LPS (Capto 50-LPS), and 100 mg kg-1 captopril - LPS (Capto 100-LPS). Behavioral tests including open-field (OF), elevated plus maze (EPM) and forced swimming (FS) test were performed, and the serum level of interleukin-6 (IL-6) was assessed. In OF, the number of crossings in the central zone in Capto 10-LPS, Capto 50-LPS, and Capto 100-LPS groups was higher than that of the sham group. In EPM, the open arm entry numbers in the sham group were lower compared to the control group. Furthermore, pretreatment by captopril increased the entries to the open arms. In FS test, the immobility time of the sham group was longer than that of the control group. In Capto 10-LPS, Capto 50-LPS, and Capto 100-LPS groups, immobility was shorter compared to the sham group. In addition, the IL-6 level was higher in the sham group compared to the control group, and treatment with 50 and 100 mg kg-1 of captopril restored the IL-6 level in comparison with the sham group. Results confirmed that pretreatment with captopril ameliorated LPS-caused sickness behaviors and attenuated IL-6 as an inflammatory marker in the rats.

The effects of Nigella sativa on sickness behavior induced by lipopolysaccharide in male Wistar rats.

OBJECTIVE: Neuroimmune factors contribute on the pathogenesis of sickness behaviors. Nigella sativa (NS) has anti-inflammatory, anti-anxiety and anti-depressive effects. In the present study, the effect of NS hydro-alcoholic extract on sickness behavior induced by lipopolysaccharide (LPS) was investigated. MATERIALS AND METHODS: The rats were divided into five groups (n=10 in each): (1) control (saline), (2) LPS (1 mg/kg, administered two hours before behavioral tests), (3-5) LPS-Nigella sativa 100 , 200 and 400 mg/kg (LPS-NS 100, LPS-NS 200 and LPS-NS 400, respectively). Open- field (OF), elevated plus maze (EPM) and forced swimming test (FST) were performed. RESULTS: In OF, LPS reduced the peripheral crossing, peripheral distance, total crossing and total distance compared to control (p<0.01- p<0.001). The central crossing, central distance and central time in LPS-NS 100, LPS-NS200 and LPS-NS 400 groups were higher than LPS (p<0.01- p<0.001). In EPM, LPS decreased the open arm entries, open arm time and closed arm entries while increased the closed time compared to control (p<0.001). Pretreatment by NS extract reversed the effects of LPS (p<0.05- p<0.001). In FST, LPS increased the immobility time while, decreased the climbing and active times compared to control (p<0.05- p<0.001). In LPS-NS 100, LPS-NS 200 and LPS-NS 400 groups the immobility time was less while, the active and climbing times were more than those of LPS (p<0.05- p<0.001). CONCLUSION: The results of the present study showed that the hydro-alcoholic extract of NS reduced the LPS-induced sickness behaviors in rats. Further investigations are required for better understanding the responsible compound (s) and the underlying mechanism(s).

Tamoxifen antagonizes the effects of ovarian hormones to induce anxiety and depression-like behavior in rats.

The effects of tamoxifen (TAM) on anxiety and depression-like behavior in ovariectomized (OVX) and naïve female rats were investigated. The animals were divided into Sham-TAM, OVX-TAM, Sham and OVX groups. Tamoxifen (1 mg/kg) was administered for 4 weeks. In the forced swimming test, the immobility times in the OVX and Sham-TAM groups were higher than in the Sham group. In the open field, the numbers of central crossings in the OVX and Sham-TAM groups were lower than the number in the Sham group, and the number of peripheral crossings in the OVX group was lower than the number in the Sham group. In the elevated plus maze, the numbers of entries to the open arm among the animals in the Sham-TAM and OVX groups were lower than the number in the Sham group, while the number of entries to the open arm in the OVX-TAM group was higher than the number in the OVX group. It was shown that deletion of ovarian hormones induced anxiety and depression-like behavior. Administration of tamoxifen in naïve rats led to anxiety and depression-like behavior that was comparable with the effects of ovarian hormone deletion. It can be suggested that tamoxifen antagonizes the effects of ovarian hormones. It also seems that tamoxifen has anxiolytic effects on ovariectomized rats.

Deletion of ovarian hormones induces a sickness behavior in rats comparable to the effect of lipopolysaccharide.

Neuroimmune factors have been proposed as the contributors to the pathogenesis of sickness behaviors. The effects of female gonadal hormones on both neuroinflammation and depression have also been well considered. In the present study, the capability of deletion of ovarian hormones to induce sickness-like behaviors in rats was compared with the effect lipopolysaccharide (LPS). The groups were including Sham, OVX, Sham-LPS, and OVX-LPS. The Sham-LPS and OVX-LPS groups were treated with LPS (250 µg/kg) two hours before conducting the behavioral tests. In the forced swimming (FST), the immobility times in both OVX and Sham-LPS groups were higher than that of Sham (P < 0.001). In open-field (OP) test, the central crossing number by OVX and Sham-LPS groups were lower than Sham (P < 0.001) while there were no significant differences between OVX-LPS and OVX groups. In elevated plus maze (EPM), the percent of entries to the open arm by both OVX and Sham-LPS groups was lower than that of Sham group (P < 0.001). The results of present study showed that deletion of ovarian hormones induced sickness behaviors in rats which were comparable to the effects of LPS. Moreover, further investigations are required in order to better understand the mechanism(s) involved.

Tamoxifen antagonizes the effects of ovarian hormones to induce anxiety and depression-like behavior in rats / Tamoxifeno antagoniza os efeitos dos hormônios ovarianos que induzem comportamento similar a ansiedade e depressão em ratos

The effects of tamoxifen (TAM) on anxiety and depression-like behavior in ovariectomized (OVX) and naïve female rats were investigated. The animals were divided into Sham-TAM, OVX-TAM, Sham and OVX groups. Tamoxifen (1 mg/kg) was administered for 4 weeks. In the forced swimming test, the immobility times in the OVX and Sham-TAM groups were higher than in the Sham group. In the open field, the numbers of central crossings in the OVX and Sham-TAM groups were lower than the number in the Sham group, and the number of peripheral crossings in the OVX group was lower than the number in the Sham group. In the elevated plus maze, the numbers of entries to the open arm among the animals in the Sham-TAM and OVX groups were lower than the number in the Sham group, while the number of entries to the open arm in the OVX-TAM group was higher than the number in the OVX group. It was shown that deletion of ovarian hormones induced anxiety and depression-like behavior. Administration of tamoxifen in naïve rats led to anxiety and depression-like behavior that was comparable with the effects of ovarian hormone deletion. It can be suggested that tamoxifen antagonizes the effects of ovarian hormones. It also seems that tamoxifen has anxiolytic effects on ovariectomized rats.

Foram investigados os efeitos do tamoxifeno (TAM) no comportamento semelhante a ansiedade de depressão de ratas ooforectomizadas (OVX) e controles. Os animais foram divididos em Sham-TAM, OVX-TAM, Sham e OVX groups. Tamoxifeno (1 mg/kg) foi administrado por quatro semanas. No teste de natação forçada, os tempos de imobilidade nos grupos OVX e Sham-TAM foram maiores que aqueles do grupo Sham. No campo aberto, os números de cruzamento no centro nos grupos OVX e Sham-TAM foram menores que aquele do grupo Sham, e o número dos cruzamentos na periferia no grupo OVX foi menor que o número no grupo Sham. No labirinto elevado, os números de entradas com braços abertos entre os animais nos grupos Sham-TAM e OVX foram menores do que aqueles do grupo Sham, enquanto o número de entradas com os braços abertos no grupo OVX-TAM foi maior que aquele no grupo OVX. Foi observado que a deleção dos hormônios ovarianos induziu comportamento similar a ansiedade e depressão. A administração de tamoxifeno em ratos controle induziu a um comportamento que era comparável aos efeitos da deleção do hormônio ovariano. Pode ser sugerido que o tamoxifeno antagoniza os efeitos dos hormônios ovarianos. Parece também que o tamoxifeno tem efeito ansiolítico nas ratas ooforectomizadas.