ABSTRACT
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.
Subject(s)
Animals , Male , Rats , Cocaine/pharmacology , Cyclin-Dependent Kinases/metabolism , Dendrites/drug effects , Dendrites/metabolism , Dopamine Uptake Inhibitors/pharmacology , Nucleus Accumbens/drug effects , Nucleus Accumbens/enzymology , Cyclin-Dependent Kinases/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Microscopy, Confocal , Neurons/drug effects , Neurons/metabolism , Purines/pharmacology , Rats, Sprague-DawleyABSTRACT
The effects of a high estradiol dose on memory and on nitric oxide metabolites in hippocampal tissues were investigated. Sham-Est and OVX-Est Groups were treated with 4 mg/kg of estradiol valerate for 12 weeks. Time latency and path length were significantly higher in the Sham-Est and OVX-Est Groups than in the Sham and OVX Groups, respectively (p<0.001). The animals in the Sham-Est and OVX-Est Groups spent lower time in the target quadrant (Q1) than those of the Sham and OVX Groups during the probe trial test (p<0.05 and <0.001, respectively). Significantly lower nitric oxide metabolite levels in the hippocampi of the Sham-Est and OVX-Est Groups were observed than in the Sham and OVX ones (p<0.001). These results suggest that decreased nitric oxide levels in the hippocampus may play a role in the learning and memory deficits observed after treatment with a high dose of estradiol, although the precise underlying mechanisms remain to be elucidated.
Os efeitos de uma alta dose de estradiol na memória e nos metabólitos do óxido nítrico de tecidos hipocampais foram estudados. Os Grupos Sham-Est e OVX-Est foram tratados com 4 mg/kg de valerato de estradiol por 12 semanas. O tempo de latência e o comprimento do caminho foram significativamente maiores nos Grupos Sham-Est e OVX-Est em relação aos Grupos Sham e OVX, respectivamente (p<0,001). Os animais dos Grupos Sham-Est e OVX-Est passaram menos tempo na meta do quadrante (Q1) do que aqueles dos Grupos Sham e OVX durante o teste inicial (p<0,05 e <0,001, respectivamente). Níveis significativamente menores de metabólitos do óxido nítrico foram observados nos hipocampos dos Grupos Sham-Est e OVX-Est em relação aos Grupos Sham e OVX (p<0,001). Esses resultados sugerem que os níveis diminuídos de óxido nítrico no hipocampo podem ter um papel nos déficits de aprendizado e de memória, que são observados após tratamento com alta dose de estradiol, embora os mecanismos específicos envolvidos nestes achados ainda precisam ser elucidados.
Subject(s)
Animals , Female , Humans , Rats , Contraceptive Agents/administration & dosage , Estradiol/analogs & derivatives , Hippocampus/metabolism , Learning Disabilities/etiology , Memory Disorders/etiology , Nitric Oxide/metabolism , Analysis of Variance , Dose-Response Relationship, Drug , Estradiol/administration & dosage , Hippocampus/drug effects , Learning Disabilities/metabolism , Maze Learning/drug effects , Memory Disorders/metabolism , Memory/drug effects , Nitric Oxide/biosynthesis , Ovariectomy , Random Allocation , Rats, WistarABSTRACT
Different effects of scopolamine on learning, memory, and nitric oxide (NO) metabolites in hippocampal tissues of ovariectomized (OVX) and sham-operated rats were investigated. The animals in the Sham-Scopolamine (Sham-Sco) and OVX-Scopolamine (OVX-Sco) Groups were treated with 2 mg/kg scopolamine before undergoing the Morris water maze, while the animals in the Sham and OVX Groups received saline. The time latency and path length were significantly higher in both the Sham-Sco and the OVX-Sco Groups, in comparison with the Sham and OVX Groups, respectively (p<0.001). Significantly lower NO metabolite levels in the hippocampi of the Sham-Sco Group were observed, compared with the Sham Group (p<0.001), while there was no significant difference between the OVX-Sco and OVX Groups. The decreased NO level in the hippocampus may play a role in the learning and memory deficits induced by scopolamine. However, it seems that the effect of scopolamine on hippocampal NO differs between situations of presence and absence of ovarian hormones.
Diferentes efeitos da escopolamina no aprendizado, na memória e nos níveis dos metabólitos do óxido nítrico (ON) no tecido hipocampal de ratas ovariectomizadas (OVX) e controles com cirurgia sem ooforectomia (Grupo Sham) foram investigados. Os animais dos grupos Sham-Escopolamina (Sham-Sco) e OVX-Escopolamina (OVX-Sco) foram tratados com escopolamina 2 mg/kg antes de entrar no labirinto aquático de Morris, enquanto aqueles dos grupos Sham e OVX receberam solução salina. A latência de tempo e o comprimento do caminho foram significativamente maiores nos Grupos Sham-Sco e OVX-Sco em comparação com os grupos Sham e OVX, respectivamente (p<0,001). Foram observados níveis significativamente mais baixos de metabólitos do ON nos hipocampos do Grupo Sham-Sco em comparação aos níveis do Sham (p<0,001), enquanto não foi observada diferença significativa entre os Grupos OVX-Sco e OVX. A diminuição do nível de ON no hipocampo pode ter um papel no aprendizado e nos déficits de memória induzidos pela escopolamina. No entanto, parece que este efeito da escopolamina no ON hipocampal é diferente em situações de presença ou ausência de hormônios ovarianos.
Subject(s)
Animals , Female , Rats , Cholinergic Antagonists/pharmacology , Hippocampus/chemistry , Maze Learning/drug effects , Memory/drug effects , Nitric Oxide/metabolism , Scopolamine/pharmacology , Hippocampus/drug effects , Ovariectomy , Rats, Wistar , Reaction Time , Time FactorsABSTRACT
INTRODUCTION: The role of ovarian hormones and nitric oxide in learning and memory has been widely investigated. OBJECTIVE: The present study was carried out to evaluate the effect of the nitric oxide synthase (NOS) inhibitor, N (G)-nitro-L-arginine methyl ester (L-NAME), on the ability of estradiol to improve learning in OVX rats using the Morris water maze. METHODS: Forty rats were divided into five groups: (1) ovariectomized (OVX), (2) ovariectomized-estradiol (OVX-Est), (3) ovariectomized-L-NAME 10 (OVX-LN 10), (4) ovariectomized-L-NAME 50 (OVX-LN 50) and (5) ovariectomized-estradiol-L-NAME 50 (OVX-Est-LN 50). The animals in the OVX-Est group were treated with a weekly injection of estradiol valerate (2 mg/kg; i.m.). The OVX-LN 10 and OVX-LN 50 groups were treated with daily injections of 10 and 50 mg/kg L-NAME (i.p.), respectively. The animals in the OVX-Est-LN 50 group received a weekly injection of estradiol valerate and a daily injection of 50 mg/kg L-NAME. After 8 weeks, all animals were tested in the Morris water maze. RESULTS: The animals in the OVX-Est group had a significantly lower latency in the maze than the OVX group (p<0.001). There was no significant difference in latency between the OVX-LN 10 and OVX-LN 50 groups in comparison with the OVX group. The latency in the OVX-Est-LN 50 group was significantly higher than that in the OVX-Est group (p<0.001). CONCLUSION: These results show that L-NAME treatment attenuated estradiol-mediated enhancement of spatial learning and memory in OVX rats, but it had no significant effect in OVX rats without estrogen, suggesting an interaction of nitric oxide and estradiol in these specific brain functions.