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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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Social interaction test.(A) The juvenile exploration ratio represents time spent exploring the juvenile rat over the total time spent exploring the juvenile rat and the object, evaluated during the 10 min session of the test. Both SE models regardless of the strain, but especially LIP-treated animals, showed decreased preference for exploration of the juvenile conspecific. (B) Total distance traveled in the social interaction test. The results are presented as the mean ± SEM. * P<0.05; *** P<.0001; +++ P<.0001. Abbreviations: W: Wistar; SD: Sprague-Dawley; LIP: lithium-pilocarpine; KA: kainic acid.
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pone-0038959-g002: Social interaction test.(A) The juvenile exploration ratio represents time spent exploring the juvenile rat over the total time spent exploring the juvenile rat and the object, evaluated during the 10 min session of the test. Both SE models regardless of the strain, but especially LIP-treated animals, showed decreased preference for exploration of the juvenile conspecific. (B) Total distance traveled in the social interaction test. The results are presented as the mean ± SEM. * P<0.05; *** P<.0001; +++ P<.0001. Abbreviations: W: Wistar; SD: Sprague-Dawley; LIP: lithium-pilocarpine; KA: kainic acid.

Mentions: Sociability was subsequently assessed using a social interaction test. A factorial ANOVA on the ratio of juvenile vs. object exploration indicated a similar lack of effect of strain [F(1, 44) = 1.16, n.s.] or strain x treatment interaction [F(2, 44) = 0.02, n.s.], but a significant effect of the treatment factor [F(2, 44) = 25.04, P<0.0001] (Fig. 2A). Further paired factorial ANOVAs including the two treatment groups revealed that this effect was due to both SE-treated groups showing a significantly lower exploration ratio than the controls [LIP: F(1, 27) = 37.82, P<0.0001; KA: F(1, 30) = 5.88, P<0.05]; additionally, the low exploration ratio of LIP-treated animals was significantly different from that of KA-treated rats [F(1, 27) = 20.01, P<0.0001]. These treatment differences in exploration ratio were observed despite a lack of treatment effect in total locomotor behavior [F(2, 44) = 1.36, n.s.](Fig. 2B). Locomotion data, however, depicted an effect of strain [F(1, 44) = 5.33, P<0.05], reflecting a mild increase in distance moved by Wistar SE-rats. No strain x treatment interaction was found for locomotor behavior in this test [F(2, 44) = 1.73, n.s.]. Overall, these results indicate reduced motivation for social contact in both SE models irrespective of the strain, with LIP-treated animals being particularly affected.


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)

Social interaction test.(A) The juvenile exploration ratio represents time spent exploring the juvenile rat over the total time spent exploring the juvenile rat and the object, evaluated during the 10 min session of the test. Both SE models regardless of the strain, but especially LIP-treated animals, showed decreased preference for exploration of the juvenile conspecific. (B) Total distance traveled in the social interaction test. The results are presented as the mean ± SEM. * P<0.05; *** P<.0001; +++ P<.0001. Abbreviations: W: Wistar; SD: Sprague-Dawley; LIP: lithium-pilocarpine; KA: kainic acid.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0038959-g002: Social interaction test.(A) The juvenile exploration ratio represents time spent exploring the juvenile rat over the total time spent exploring the juvenile rat and the object, evaluated during the 10 min session of the test. Both SE models regardless of the strain, but especially LIP-treated animals, showed decreased preference for exploration of the juvenile conspecific. (B) Total distance traveled in the social interaction test. The results are presented as the mean ± SEM. * P<0.05; *** P<.0001; +++ P<.0001. Abbreviations: W: Wistar; SD: Sprague-Dawley; LIP: lithium-pilocarpine; KA: kainic acid.
Mentions: Sociability was subsequently assessed using a social interaction test. A factorial ANOVA on the ratio of juvenile vs. object exploration indicated a similar lack of effect of strain [F(1, 44) = 1.16, n.s.] or strain x treatment interaction [F(2, 44) = 0.02, n.s.], but a significant effect of the treatment factor [F(2, 44) = 25.04, P<0.0001] (Fig. 2A). Further paired factorial ANOVAs including the two treatment groups revealed that this effect was due to both SE-treated groups showing a significantly lower exploration ratio than the controls [LIP: F(1, 27) = 37.82, P<0.0001; KA: F(1, 30) = 5.88, P<0.05]; additionally, the low exploration ratio of LIP-treated animals was significantly different from that of KA-treated rats [F(1, 27) = 20.01, P<0.0001]. These treatment differences in exploration ratio were observed despite a lack of treatment effect in total locomotor behavior [F(2, 44) = 1.36, n.s.](Fig. 2B). Locomotion data, however, depicted an effect of strain [F(1, 44) = 5.33, P<0.05], reflecting a mild increase in distance moved by Wistar SE-rats. No strain x treatment interaction was found for locomotor behavior in this test [F(2, 44) = 1.73, n.s.]. Overall, these results indicate reduced motivation for social contact in both SE models irrespective of the strain, with LIP-treated animals being particularly affected.

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