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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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Related in: MedlinePlus

Plasma corticosterone levels assessed before (pre-behavioral phase) and after (post-behavioral phase) the behavioral tests.The results are presented as the mean ± SEM. ** P<0.01 vs. the corresponding pre-behavioral data from the same group. For this analysis, strains were pooled. Abbreviations: LIP: lithium-pilocarpine; KA: kainic acid.
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pone-0038959-g004: Plasma corticosterone levels assessed before (pre-behavioral phase) and after (post-behavioral phase) the behavioral tests.The results are presented as the mean ± SEM. ** P<0.01 vs. the corresponding pre-behavioral data from the same group. For this analysis, strains were pooled. Abbreviations: LIP: lithium-pilocarpine; KA: kainic acid.

Mentions: The analysis of plasma corticosterone concentrations showed a main effect for the time at which samples were taken (pre- and post-behavioral) as well as an interaction between sampling and group [F(1, 26) = 8.43, P<0.01 and F(2, 26) = 7.41, P<0.01, respectively] but did not show a main effect for the group [F(2, 26) = 1.01, P = 0.38]. Subsequent Bonferroni-corrected pair-wise comparisons between each pair of samples for each group indicated that LIP-treated rats had a significantly higher post-behavioral corticosterone concentration (t = -4.60, df = 7, P<0.01) than their initial corticosterone concentration (Fig. 4). Interestingly, KA-treated animals did not show differences between the two samples (t = 0.38, df = 13, P = 0.71), similar to control rats (t = -0.66, df = 7, P = 0.53).


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)

Plasma corticosterone levels assessed before (pre-behavioral phase) and after (post-behavioral phase) the behavioral tests.The results are presented as the mean ± SEM. ** P<0.01 vs. the corresponding pre-behavioral data from the same group. For this analysis, strains were pooled. Abbreviations: LIP: lithium-pilocarpine; KA: kainic acid.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0038959-g004: Plasma corticosterone levels assessed before (pre-behavioral phase) and after (post-behavioral phase) the behavioral tests.The results are presented as the mean ± SEM. ** P<0.01 vs. the corresponding pre-behavioral data from the same group. For this analysis, strains were pooled. Abbreviations: LIP: lithium-pilocarpine; KA: kainic acid.
Mentions: The analysis of plasma corticosterone concentrations showed a main effect for the time at which samples were taken (pre- and post-behavioral) as well as an interaction between sampling and group [F(1, 26) = 8.43, P<0.01 and F(2, 26) = 7.41, P<0.01, respectively] but did not show a main effect for the group [F(2, 26) = 1.01, P = 0.38]. Subsequent Bonferroni-corrected pair-wise comparisons between each pair of samples for each group indicated that LIP-treated rats had a significantly higher post-behavioral corticosterone concentration (t = -4.60, df = 7, P<0.01) than their initial corticosterone concentration (Fig. 4). Interestingly, KA-treated animals did not show differences between the two samples (t = 0.38, df = 13, P = 0.71), similar to control rats (t = -0.66, df = 7, P = 0.53).

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