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Sleep-related epilepsy in a Long-Evans hooded rat model of depression

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Abstract

Introduction

Neonatal treatment with clomipramine (CLI) has been shown to have reliable behavioral and biological changes that mimic major symptomatic and biochemical changes found in depression. This paper further explores a common feature of depression, the comorbidity of seizure activity and depressive behaviors in this mode.

Methods

Rat pups were neonatally treated with 40 mg/kg/day of CLI from postnatal day 8 through 21. In adulthood, they were instrumented with electroencephalographic (EEG) and electromyographic (EMG) electrodes for 24 h of polysomnogram (PSG) recordings. PSG data were analyzed for: (1) sleep-wake cycle; (2) spectral power; and (3) epileptiform activity, including NREM-to-REM transition (NRT) bursts.

Results

Neonatal treatment with CLI reliably produces enhanced levels of REM (p < 0.01) and reduced sexual activity (p < 0.05). Theta power was enhanced during NREM sleep in the CLI group (p = 0.02). CLI-treated animals experienced increased frequency at the NRT (p < 0.01), as well as additional epileptiform activity of continuous (CTS; p < 0.05) and petite-continuous (P-CTS; p < 0.01) types, across the sleep–wake cycle. There is a strong temporal correlation with increased REM sleep duration, increased frequency of NRT bursts, and increased theta power during NREM sleep in CLI-treated animals.

Discussion

Neonatal CLI-treated animals experienced significantly more epileptiform activity as a whole, in addition to comorbid features of depression in adulthood. Neonatal exposure to CLI will not only produce depressive phenotype but may also enhance risk for epilepsy in some individuals. This warrants further investigation into currently acceptable medicinal use in humans.

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Acknowledgements

This study was supported by the VA Merit award, NIH training grant T32-5THL007913-10, and Louis Stokes Cleveland VA Medical Service. The authors would like to thank Dr. van Lunteren for lending his equipment to us to measure locomotor activity and lab members who gave valuable feedback or contributed to this project: Afaf Akladious, Jiejin Zhang, Phil Smith, and Yufen Hu.

Conflicts of interest

None of the authors has any conflict of interest to disclose.

We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

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Author notes

  1. Angela L. McDowell

    Present address: Division of Pulmonary, Allergy and Critical Care, University of Pittsburgh, Pittsburgh, USA

Authors and Affiliations

  1. Division of Pulmonary, Critical Care and Sleep Medicine, Case Western Reserve University, Cleveland, OH, USA

    Angela L. McDowell, Kingman P. Strohl & Pingfu Feng

  2. Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA

    Kingman P. Strohl & Pingfu Feng

  3. CWRU/VA Medical Center, Research Sec. Rm K217, 10701 East BLVD, Cleveland, OH, 44106, USA

    Pingfu Feng

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  1. Angela L. McDowell
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Correspondence to Pingfu Feng.

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McDowell, A.L., Strohl, K.P. & Feng, P. Sleep-related epilepsy in a Long-Evans hooded rat model of depression. Sleep Breath 16, 1181–1191 (2012). https://doi.org/10.1007/s11325-011-0630-x

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  • DOI: https://doi.org/10.1007/s11325-011-0630-x

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