ABSTRACT
Melatonin is involved in the control of circadian and seasonal rhythmicity, possesses potent antioxidant activity, and exerts a neuroprotective and anticonvulsant effect. Spontaneously hypertensive rats (SHRs) are widely accepted as an experimental model of essential hypertension with hyperactivity, deficient sustained attention, and alterations in circadian autonomic profiles. The purpose of the present study was to determine whether melatonin treatment during epileptogenesis can prevent the deleterious consequences of status epilepticus (SE) in SHRs in the kainate (KA) model of temporal lobe of epilepsy (TLE). Spontaneous recurrent seizures (SRSs) were EEG- and video-recorded during and after the treatment protocol. Melatonin (10mg/kg diluted in drinking water, 8weeks) increased the seizure-latent period, decreased the frequency of SRSs, and attenuated the circadian rhythm of seizure activity in SHRs. However, melatonin was unable to affect the disturbed diurnal rhythms and behavioral changes associated with epilepsy, including the decreased anxiety level, depression, and impaired spatial memory. Melatonin reduced neuronal damage specifically in the CA1 area of the hippocampus and piriform cortex and decreased hippocampal serotonin (5-HT) levels both in control and epileptic SHRs. Although long-term melatonin treatment after SE shows a potential to attenuate seizure activity and neuronal loss, it is unable to restore epilepsy-associated behavioral abnormalities in SHRs.
Subject(s)
Antioxidants/therapeutic use , Behavior, Animal/drug effects , Brain/pathology , Epilepsy, Temporal Lobe/drug therapy , Epilepsy, Temporal Lobe/physiopathology , Melatonin/therapeutic use , Animals , Antioxidants/pharmacology , Blood Pressure/drug effects , Body Weight/drug effects , Brain/drug effects , Circadian Rhythm/drug effects , Disease Models, Animal , Epilepsy, Temporal Lobe/chemically induced , Exploratory Behavior/drug effects , Food Preferences/drug effects , Kainic Acid/toxicity , Male , Maze Learning/drug effects , Melatonin/pharmacology , Rats , Rats, Inbred SHR , Serotonin/metabolism , Swimming/psychology , Time FactorsABSTRACT
The purpose of this study was to explore whether the kainate (KA) model of temporal lobe epilepsy (TLE) can be used as a model of comorbid epilepsy and depression to study diurnal behavioral variations in rats. Development of chronic epilepsy was confirmed by the detection of spontaneous motor seizures (SMS) with video monitoring (24 hours/3-5 months after status epilepticus [SE]). KA-treated spontaneously hypertensive rats (SHRs) exhibited higher seizure frequency than Wistar rats during the light phase in the fourth and fifth months after SE. Although epileptic Wistar rats showed depression-like behavior and reduced anxiety mostly during the light phase, there were no diurnal variations in depression-like patterns in SHRs. Anxiety levels of control and epileptic SHRs were similar. Decreases in serotonin, tryptophan, and dopamine concentrations in the hippocampus were detected in epileptic Wistar rats compared with naive controls. However, monoamine levels of epileptic SHRs were close to those of their controls. Wistar rats and SHRs develop stable depression-like behavior during the chronic epileptic phase with strain-dependent diurnal differences.
Subject(s)
Chronobiology Disorders/etiology , Circadian Rhythm/physiology , Depression/etiology , Epilepsy, Temporal Lobe/complications , Analysis of Variance , Animals , Avoidance Learning/drug effects , Behavior, Animal/drug effects , Blood Pressure/drug effects , Catecholamines/metabolism , Chromatography, High Pressure Liquid/methods , Circadian Rhythm/drug effects , Disease Models, Animal , Epilepsy, Temporal Lobe/chemically induced , Escape Reaction/drug effects , Hippocampus/metabolism , Kainic Acid/adverse effects , Male , Maze Learning/drug effects , Rats , Rats, Inbred SHR , Rats, Wistar , Statistics, Nonparametric , Sucrose/metabolism , Swimming/psychology , Time FactorsABSTRACT
Attention deficit hyperactivity disorder (ADHD) can coexist with epilepsy. Spontaneously hypertensive rats (SHRs) are considered to model ADHD with overactivity, impulsiveness, deficient sustained attention, and alterations in circadian autonomic profiles. The present study explored spontaneous recurrent seizures (SRSs) and behavioral diurnal activity rhythms in normotensive Wistar rats and SHRs in the kainate model of epilepsy. Rats were video monitored (24 h/3 months) to detect SRSs. SHRs manifested a lower seizure frequency during the light phase in the 8th and 10th weeks and a lower frequency of SRSs during the night phase accompanied by attenuated responses in hyperexcitability tests. Both epileptic strains were hyperactive, with lower anxiety levels, and their diurnal rhythms were abolished. Epileptic Wistar rats and SHRs exhibited less exploration during the dark phase. This study suggests that SHRs may be useful in modeling some aspects (particularly hypertension-related diurnal rhythm disturbance) of behavior associated with epilepsy.