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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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Anhedonia test.(A) Saccharin consumption and (B) saccharin preference was assessed in all groups simultaneously. The data for saccharin consumption per 100 g body weight (A) showed increased saccharin intake in LIP-treated rats compared with controls and KA-treated animals, regardless of the strain. The data for saccharin preference (B) indicated no differences between groups. The results are presented as the mean ± SEM. # P<0.05; ** P<0.01. Abbreviations: W: Wistar; SD: Sprague-Dawley; LIP: lithium-pilocarpine; KA: kainic acid.
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pone-0038959-g001: Anhedonia test.(A) Saccharin consumption and (B) saccharin preference was assessed in all groups simultaneously. The data for saccharin consumption per 100 g body weight (A) showed increased saccharin intake in LIP-treated rats compared with controls and KA-treated animals, regardless of the strain. The data for saccharin preference (B) indicated no differences between groups. The results are presented as the mean ± SEM. # P<0.05; ** P<0.01. Abbreviations: W: Wistar; SD: Sprague-Dawley; LIP: lithium-pilocarpine; KA: kainic acid.

Mentions: A factorial ANOVA on the saccharin consumption in the anhedonia test (Fig. 1A) indicated a lack of effect of strain [F(1, 32) = 0.93, n.s.] or strain x treatment interaction [F(2, 32) = 0.91, n.s.] but a significant effect of the treatment factor [F(2, 32) = 7.43, P<0.01]. Further paired factorial ANOVAs including two treatment groups revealed that the treatment effect was mainly due to a significantly increased saccharin intake in the LIP-treated rats compared with the KA-treated rats [F(1, 22) = 19.78, P<0.01] and controls [F(1, 18) = 5.03, P<0.05]. No differences were observed between KA-treated and control rats [F(1, 24) = 0.75, n.s.]. When saccharin preference was evaluated (Fig. 1B), a factorial ANOVA indicated a lack of effect of strain [F(1, 32) = 3.04, n.s.], treatment [F(2, 32) = 2.57, n.s.] or strain x treatment interaction [F(2, 32) = 0.4, n.s.]. Differences in body weight cannot explain these results because all groups had similar weights at the beginning of behavioral testing (Control W: 430.19±16.58 mg, Control SD: 423.56±12.59 mg, LIP-W: 460.33±27.30 mg, LIP-SD: 420.56±7.21 mg, KA-W: 462.50±14.28 mg, KA-SD: 430.57±10.51 mg, F(2, 49) = 0.56, n.s.). Moreover, LIP-treated rats did not drink more water than the other groups (data not shown). Overall, these results suggest increased motivation in the LIP-treated animals, irrespective of the strain, to consume more saccharin than the other groups.


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)

Anhedonia test.(A) Saccharin consumption and (B) saccharin preference was assessed in all groups simultaneously. The data for saccharin consumption per 100 g body weight (A) showed increased saccharin intake in LIP-treated rats compared with controls and KA-treated animals, regardless of the strain. The data for saccharin preference (B) indicated no differences between groups. The results are presented as the mean ± SEM. # P<0.05; ** P<0.01. 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-g001: Anhedonia test.(A) Saccharin consumption and (B) saccharin preference was assessed in all groups simultaneously. The data for saccharin consumption per 100 g body weight (A) showed increased saccharin intake in LIP-treated rats compared with controls and KA-treated animals, regardless of the strain. The data for saccharin preference (B) indicated no differences between groups. The results are presented as the mean ± SEM. # P<0.05; ** P<0.01. Abbreviations: W: Wistar; SD: Sprague-Dawley; LIP: lithium-pilocarpine; KA: kainic acid.
Mentions: A factorial ANOVA on the saccharin consumption in the anhedonia test (Fig. 1A) indicated a lack of effect of strain [F(1, 32) = 0.93, n.s.] or strain x treatment interaction [F(2, 32) = 0.91, n.s.] but a significant effect of the treatment factor [F(2, 32) = 7.43, P<0.01]. Further paired factorial ANOVAs including two treatment groups revealed that the treatment effect was mainly due to a significantly increased saccharin intake in the LIP-treated rats compared with the KA-treated rats [F(1, 22) = 19.78, P<0.01] and controls [F(1, 18) = 5.03, P<0.05]. No differences were observed between KA-treated and control rats [F(1, 24) = 0.75, n.s.]. When saccharin preference was evaluated (Fig. 1B), a factorial ANOVA indicated a lack of effect of strain [F(1, 32) = 3.04, n.s.], treatment [F(2, 32) = 2.57, n.s.] or strain x treatment interaction [F(2, 32) = 0.4, n.s.]. Differences in body weight cannot explain these results because all groups had similar weights at the beginning of behavioral testing (Control W: 430.19±16.58 mg, Control SD: 423.56±12.59 mg, LIP-W: 460.33±27.30 mg, LIP-SD: 420.56±7.21 mg, KA-W: 462.50±14.28 mg, KA-SD: 430.57±10.51 mg, F(2, 49) = 0.56, n.s.). Moreover, LIP-treated rats did not drink more water than the other groups (data not shown). Overall, these results suggest increased motivation in the LIP-treated animals, irrespective of the strain, to consume more saccharin than the other groups.

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