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Different emotional disturbances in two experimental models of temporal lobe epilepsy in rats.

Inostroza M, Cid E, Menendez de la Prida L, Sandi C - PLoS ONE (2012)

Bottom Line: To address this issue, we examined the emotional sequelae of two SE models of temporal lobe epilepsy (TLE)--the lithium-pilocarpine (LIP) model and the kainic acid (KA) model--in two different rat strains (Wistar and Sprague-Dawley), which differ significantly in the pattern and extent of TLE-associated brain lesions.We found differences between LIP- and KA-treated animals in tests for depression-like and anxiety-like behaviors, as well as differences in plasma corticosterone levels.This hyperactivity in the hypothalamus-pituitary-adrenocortical (HPA) axis was highly correlated with performance in the open field test and the social interaction test, suggesting that comorbidity of epilepsy and emotional behaviors might also be related to other factors such as HPA axis function.

View Article: PubMed Central - PubMed

Affiliation: Instituto Cajal, Spanish National Research Council, Madrid, Spain.

ABSTRACT
Affective symptoms such as anxiety and depression are frequently observed in patients with epilepsy. The mechanisms of comorbidity of epilepsy and affective disorders, however, remain unclear. Diverse models are traditionally used in epilepsy research, including the status epilepticus (SE) model in rats, which are aimed at generating chronic epileptic animals; however, the implications of different SE models and rat strains in emotional behaviors has not been reported. To address this issue, we examined the emotional sequelae of two SE models of temporal lobe epilepsy (TLE)--the lithium-pilocarpine (LIP) model and the kainic acid (KA) model--in two different rat strains (Wistar and Sprague-Dawley), which differ significantly in the pattern and extent of TLE-associated brain lesions. We found differences between LIP- and KA-treated animals in tests for depression-like and anxiety-like behaviors, as well as differences in plasma corticosterone levels. Whereas only LIP-treated rats displayed increased motivation to consume saccharin, both SE models led to reduced motivation for social contact, with LIP-treated animals being particularly affected. Evaluation of behavior in the open field test indicated very low levels of anxiety in LIP-treated rats and a mild decrease in KA-treated rats compared to controls. After exposure to a battery of behavioral tests, plasma corticosterone levels were increased only in LIP-treated animals. This hyperactivity in the hypothalamus-pituitary-adrenocortical (HPA) axis was highly correlated with performance in the open field test and the social interaction test, suggesting that comorbidity of epilepsy and emotional behaviors might also be related to other factors such as HPA axis function. Our results indicate that altered emotional behaviors are not inherent to the epileptic condition in experimental TLE; instead, they likely reflect alterations in anxiety levels related to model-dependent dysregulation of the HPA axis.

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Statistical correlations (including all animals) between post-behavioral corticosterone levels and behavioral indices obtained in the social interaction and open field tasks.(A) Correlation between behavioral parameters in the open field and social interaction test. Symbol code: (•) control Wistar, (○) control Sprague-Dawley, (▪) lithium-pilocarpine Wistar, (□) lithium-pilocarpine Sprague-Dawley, (▴) kainate Wistar and (Δ) kainate Sprague-Dawley. (B) Correlation between the exploration in the inner zone in the open field and the post-behavioral corticosterone levels. (C) Correlation between the juvenile exploration ratio in the social interaction test and post-behavioral corticosterone level.
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pone-0038959-g005: Statistical correlations (including all animals) between post-behavioral corticosterone levels and behavioral indices obtained in the social interaction and open field tasks.(A) Correlation between behavioral parameters in the open field and social interaction test. Symbol code: (•) control Wistar, (○) control Sprague-Dawley, (▪) lithium-pilocarpine Wistar, (□) lithium-pilocarpine Sprague-Dawley, (▴) kainate Wistar and (Δ) kainate Sprague-Dawley. (B) Correlation between the exploration in the inner zone in the open field and the post-behavioral corticosterone levels. (C) Correlation between the juvenile exploration ratio in the social interaction test and post-behavioral corticosterone level.

Mentions: First, we evaluated whether there was correlation between anxiety- and depression-like behaviors. We found a negative correlation (r = -0.565, P<0.01) between the anxiety-like measurements from the open-field (OF) and behaviors in the social interaction test (Fig. 5A). In addition, we found a positive correlation between the time spent in the central area of the OF and the post-behavioral corticosterone level (r = 0.508, P<0.01; Fig. 5B), indicating that the greater the increase in the corticosterone levels (i.e., hyperactivity of the HPA axis), the lower the anxiety (i.e., the more time spent in the central area in the OF). Again, we found a negative correlation (r = -0.452, P<0.05; Fig. 5C) between post-behavioral corticosterone concentration and performance in the social interaction test, suggesting that the functional activation of the HPA axis is negatively related to the motivation for social interaction.


Different emotional disturbances in two experimental models of temporal lobe epilepsy in rats.

Inostroza M, Cid E, Menendez de la Prida L, Sandi C - PLoS ONE (2012)

Statistical correlations (including all animals) between post-behavioral corticosterone levels and behavioral indices obtained in the social interaction and open field tasks.(A) Correlation between behavioral parameters in the open field and social interaction test. Symbol code: (•) control Wistar, (○) control Sprague-Dawley, (▪) lithium-pilocarpine Wistar, (□) lithium-pilocarpine Sprague-Dawley, (▴) kainate Wistar and (Δ) kainate Sprague-Dawley. (B) Correlation between the exploration in the inner zone in the open field and the post-behavioral corticosterone levels. (C) Correlation between the juvenile exploration ratio in the social interaction test and post-behavioral corticosterone level.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3376131&req=5

pone-0038959-g005: Statistical correlations (including all animals) between post-behavioral corticosterone levels and behavioral indices obtained in the social interaction and open field tasks.(A) Correlation between behavioral parameters in the open field and social interaction test. Symbol code: (•) control Wistar, (○) control Sprague-Dawley, (▪) lithium-pilocarpine Wistar, (□) lithium-pilocarpine Sprague-Dawley, (▴) kainate Wistar and (Δ) kainate Sprague-Dawley. (B) Correlation between the exploration in the inner zone in the open field and the post-behavioral corticosterone levels. (C) Correlation between the juvenile exploration ratio in the social interaction test and post-behavioral corticosterone level.
Mentions: First, we evaluated whether there was correlation between anxiety- and depression-like behaviors. We found a negative correlation (r = -0.565, P<0.01) between the anxiety-like measurements from the open-field (OF) and behaviors in the social interaction test (Fig. 5A). In addition, we found a positive correlation between the time spent in the central area of the OF and the post-behavioral corticosterone level (r = 0.508, P<0.01; Fig. 5B), indicating that the greater the increase in the corticosterone levels (i.e., hyperactivity of the HPA axis), the lower the anxiety (i.e., the more time spent in the central area in the OF). Again, we found a negative correlation (r = -0.452, P<0.05; Fig. 5C) between post-behavioral corticosterone concentration and performance in the social interaction test, suggesting that the functional activation of the HPA axis is negatively related to the motivation for social interaction.

Bottom Line: To address this issue, we examined the emotional sequelae of two SE models of temporal lobe epilepsy (TLE)--the lithium-pilocarpine (LIP) model and the kainic acid (KA) model--in two different rat strains (Wistar and Sprague-Dawley), which differ significantly in the pattern and extent of TLE-associated brain lesions.We found differences between LIP- and KA-treated animals in tests for depression-like and anxiety-like behaviors, as well as differences in plasma corticosterone levels.This hyperactivity in the hypothalamus-pituitary-adrenocortical (HPA) axis was highly correlated with performance in the open field test and the social interaction test, suggesting that comorbidity of epilepsy and emotional behaviors might also be related to other factors such as HPA axis function.

View Article: PubMed Central - PubMed

Affiliation: Instituto Cajal, Spanish National Research Council, Madrid, Spain.

ABSTRACT
Affective symptoms such as anxiety and depression are frequently observed in patients with epilepsy. The mechanisms of comorbidity of epilepsy and affective disorders, however, remain unclear. Diverse models are traditionally used in epilepsy research, including the status epilepticus (SE) model in rats, which are aimed at generating chronic epileptic animals; however, the implications of different SE models and rat strains in emotional behaviors has not been reported. To address this issue, we examined the emotional sequelae of two SE models of temporal lobe epilepsy (TLE)--the lithium-pilocarpine (LIP) model and the kainic acid (KA) model--in two different rat strains (Wistar and Sprague-Dawley), which differ significantly in the pattern and extent of TLE-associated brain lesions. We found differences between LIP- and KA-treated animals in tests for depression-like and anxiety-like behaviors, as well as differences in plasma corticosterone levels. Whereas only LIP-treated rats displayed increased motivation to consume saccharin, both SE models led to reduced motivation for social contact, with LIP-treated animals being particularly affected. Evaluation of behavior in the open field test indicated very low levels of anxiety in LIP-treated rats and a mild decrease in KA-treated rats compared to controls. After exposure to a battery of behavioral tests, plasma corticosterone levels were increased only in LIP-treated animals. This hyperactivity in the hypothalamus-pituitary-adrenocortical (HPA) axis was highly correlated with performance in the open field test and the social interaction test, suggesting that comorbidity of epilepsy and emotional behaviors might also be related to other factors such as HPA axis function. Our results indicate that altered emotional behaviors are not inherent to the epileptic condition in experimental TLE; instead, they likely reflect alterations in anxiety levels related to model-dependent dysregulation of the HPA axis.

Show MeSH
Related in: MedlinePlus