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


CONCLUSIONS
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.
Division of Pulmonary, Critical Care and Sleep Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Angela L
AL
McDowell
Kingman P
KP
Strohl
Pingfu
P
Feng
D000818:Animals; D000831:Animals, Newborn; D000929:Antidepressive Agents, Tricyclic / Q000633:toxicity*; D002997:Clomipramine / Q000633:toxicity*; D003866:Depressive Disorder / Q000139:chemically induced* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004569:Electroencephalography / Q000187:drug effects; D017034:Epilepsy, Frontal Lobe / Q000139:chemically induced* / Q000503:physiopathology*; D005583:Fourier Analysis; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D017286:Polysomnography; D051381:Rats; D020318:Rats, Long-Evans; D012307:Risk Factors; D012725:Sexual Behavior / Q000187:drug effects; D012815:Signal Processing, Computer-Assisted; D012893:Sleep Wake Disorders / Q000139:chemically induced* / Q000503:physiopathology*
D000929:Antidepressive Agents, Tricyclic; D002997:Clomipramine