Treatment with melatonin after status epilepticus attenuates seizure activity and neuronal damage but does not prevent the disturbance in diurnal rhythms and behavioral alterations in spontaneously hypertensive rats in kainate model of temporal lobe epilepsy.
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.
Institute of Neurobiology, Acad. G. Bonchev Str., Bl. 23, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria.
Zlatina
Z
Petkova
Institute of Neurobiology, Acad. G. Bonchev Str., Bl. 23, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria. Electronic address: janetchekalarova@gmail.com.
Jana
J
Tchekalarova
Institute of Neurobiology, Acad. G. Bonchev Str., Bl. 23, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria.
Daniela
D
Pechlivanova
Institute of Neurobiology, Acad. G. Bonchev Str., Bl. 23, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria.
Slavianka
S
Moyanova
Institute of Neurobiology, Acad. G. Bonchev Str., Bl. 23, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria.
Lidia
L
Kortenska
Institute of Neurobiology, Acad. G. Bonchev Str., Bl. 23, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria.
Rumiana
R
Mitreva
Institute of Neurobiology, Acad. G. Bonchev Str., Bl. 23, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria.
Deyan
D
Popov
Institute of Neurobiology, Acad. G. Bonchev Str., Bl. 23, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria.
Petya
P
Markova
Institute of Neurobiology, Acad. G. Bonchev Str., Bl. 23, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria.
Valentin
V
Lozanov
Institute of Neurobiology, Acad. G. Bonchev Str., Bl. 23, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria.
Dimitrina
D
Atanasova
Institute of Neurobiology, Acad. G. Bonchev Str., Bl. 23, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria.
Nikolai
N
Lazarov
Institute of Neurobiology, Acad. G. Bonchev Str., Bl. 23, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria.
Alexander
A
Stoynev
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D002940:Circadian Rhythm / Q000187:drug effects; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D005106:Exploratory Behavior / Q000187:drug effects; D005518:Food Preferences / Q000187:drug effects; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008550:Melatonin / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D012701:Serotonin / Q000378:metabolism; D013550:Swimming / Q000523:psychology; D013997:Time Factors
D000975:Antioxidants; D012701:Serotonin; D008550:Melatonin; D007608:Kainic Acid
5-HT; ABP; BL; C; DA; DNA; DWRME; Diurnal rhythms; EEG; EPM; FST; HPLC; Hip; KA; Kainate model of temporal lobe epilepsy; Mel; Melatonin; OF; PT; Pir; RAM; RME; SCN; SCT; SE; SHRs; SRSs; SWDs; Spontaneous hypertensive rats; TLE; Veh; WM; arterial blood pressure; basolateral nucleus; control; deoxyribonucleic acid; dopamine; electroencephalography; elevated plus maze; forced swimming test; high-performance liquid chromatography; hippocampus; i.p.; intraperitoneally; kainic acid; melatonin; open field; pars tuberalis; piriform cortex; radial arm maze; reference memory error; s.c.; serotonin; spike–wave discharges; spontaneous recurrent seizures; spontaneously hypertensive rats; status epilepticus; subcutaneously; sucrose consumption test; suprachiasmatic nucleus; temporal lobe epilepsy; vehicle; working memory error; “double” working and reference memory error