Elsevier

Neuroscience

Volume 160, Issue 2, 5 May 2009, Pages 382-393
Neuroscience

Clinical Neuroscience
Research Paper
Depression- and anxiety-like behaviors of a rat model with absence epileptic discharges

https://doi.org/10.1016/j.neuroscience.2009.02.053Get rights and content

Abstract

Depression and/or anxiety are major comorbidities of epilepsy. However, the contribution of absence epileptic discharges in psychiatric syndromes is inconclusive. This study aimed to clarify the influence of absence seizure in anxiety- and depression-like behaviors using normal Wistar rats and Long-Evans rats with spontaneous spike-wave discharges (SWDs). Anxiety-like behaviors were evaluated by the open field (OF) and elevated plus maze (EPM) tests, and depression-like behaviors by the forced swimming (FS) and sucrose consumption (SC) tests. Long-Evans rats displayed significantly higher frequency and longer duration in the open arms of the EPM and in the center zone of the OF than did Wistar rats. Normalized behavioral indexes by movement also were significantly higher in Long-Evans rats. An excess of SWD numbers was associated with lower indexes and worse movement in the two behavioral tests. Ethosuximide eliminated the seizure frequency-dependent relationship and also significantly increased all indexes of the EPM test. Additionally, Long-Evans rats revealed significantly longer immobility in the FS test and lower consumption of sucrose solution in the SC test than did Wistar rats. Meanwhile, no relationship was found between immobility of the FS test and SWD number. Ethosuximide ameliorated depression-like behavior of Long-Evans rats that was equal to that of Wistar rats. Thus, Long-Evans rats showed seizure frequency–related exacerbation in anxiety-like behavior; and they displayed a depressive propensity. Our data suggest that generalized SWDs may have distinct influences in anxious and depressive behaviors.

Section snippets

Animal preparations and recordings

Adult male Long-Evans and Wistar rats were used. Wistar rats were selected as an experimental control because they have been commonly used in previous studies (Sarkisova et al 2003, Jones et al 2008). All rats were kept in a sound-attenuated room under a 12-h light/dark cycle (07:00–19:00 h lights on) with food and water provided ad libitum. The experimental procedures were reviewed and approved by the Institutional Animal Care and Use Committee. All experiments complied with NIH (USA)

Experiment 1 comparison under a natural condition

Spontaneous SWDs (Fig. 1) were found in 39 Long-Evans rats and prominently appeared in the frontoparietal region with a small extent in the occipital area. SWDs revealed a dominant oscillation frequency of 7–12 Hz accompanied by several harmonics. Average number (96.2±16.0), duration (3.26±0.52 s), and total duration (391.6±93.1 s) of SWDs in a 1-h period on two consecutive days were measured. No spontaneous SWD was found in 15 Wistar rats during the 2-day recordings.

OF test

Long-Evans rats revealed

Discussion

The major findings of this study are (1) Long-Evans rats displayed seizure frequency-dependent exacerbation in anxiety-like behavior that was ameliorated by ESM (2). Long-Evans rats revealed a depressive propensity that was reduced by ESM. No seizure frequency–related relationship was found in depression-like behavior (3). Distinct inter-strain responses were found in anxiety- and depression-like behavior. Compared to Wistar rats, Long-Evans rats showed low anxiety but high depression. ESM

Conclusion

Aberrant SWDs had distinct influences in anxiety- and depression-like behaviors of the rat. SWDs worsened anxiety-like behavior in Long-Evans rats in a seizure frequency-dependent manner while they showed low anxiety compared to Wistar rats. Long-Evans rats displayed high depressive behavior that was not related to SWD number. Our animal model may provide an alternative choice to elucidate the operation of anxiety- and depression-related networks. Indeed, spontaneous SWDs appear in a

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