title: Anticonvulsant efficacy of melatonin in an experimental model of hyperthermic febrile seizures.
abstract: BACKGROUND
  The anticonvulsant effects of melatonin (MT) have been demonstrated in several different experimental seizure models. Thus, the present study aimed to determine the anticonvulsant efficacy of MT, the optimum time for its administration prior to the induction of a seizure, and its effective dose in a rat model of hyperthermic febrile seizures (FSs).
  
  
  METHODS
  The present study included 72 male Sprague-Dawley rat pups divided into eight groups. The seizures were induced by keeping the rats in 45 °C water and the experiments were performed in two steps. In the first step, the control group was given a vehicle injection and the study groups were given a MT injection (150 mg/kg, intraperitoneal [i.p.]) at either 5, 10, or 15 min prior to the induction of the seizure to determine the anticonvulsant effects of MT and its optimum time of administration. In the second step, a vehicle injection and three different doses of MT (80, 100, and 150 mg/kg, i.p.) were administered 15 min prior to the induction of the seizure to determine the dose at which anticonvulsant effects could be achieved. The anticonvulsant effects were assessed based on the latency of the FSs.
  
  
  RESULTS
  In the first-step experiments, the FS latency of the control group was 143.4 ± 15.3s and the latencies of the groups given melatonin at either 5, 10, or 15 min prior to the seizure were 174.2 ± 28.9, 177.4 ± 21.0, and 193.7 ± 17.6s, respectively. Compared with the control group, the latencies for each of the study groups were significantly longer (p<0.001), with the longest latency observed in the group given melatonin 15 min before the seizure. In the second-step experiments, the FS latencies of the groups that were given 80, 100, and 150 mg/kg of MT 15 min before the seizure were 238.7 ± 4.0, 240.0 ± 0.0, and 193.7 ± 17.6s, respectively. These latencies were significantly longer than those of the control group (172.3 ± 30.3s, p<0.001).
  
  
  CONCLUSIONS
  The present study demonstrated that MT exerts anticonvulsant effects in a rat model of hyperthermic FSs and achieved its optimum efficacy at a dose of 80 mg/kg when administered 15 min prior to the induction of a seizure.
authors.affiliation: Baskent University Faculty of Medicine, Department of Physiology, Ankara, Turkey. Electronic address: laydin@baskent.edu.tr.
authors.forename: Leyla
authors.initials: L
authors.lastname: Aydin
authors.affiliation: Baskent University Faculty of Medicine, Department of Physiology, Ankara, Turkey.
authors.forename: Nimet Unay
authors.initials: NU
authors.lastname: Gundogan
authors.affiliation: Baskent University Faculty of Medicine, Department of Biostatistics, Ankara, Turkey.
authors.forename: Canan
authors.initials: C
authors.lastname: Yazici
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D006979:Hyperthermia, Induced / Q000009:adverse effects*; D008297:Male; D008550:Melatonin / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012640:Seizures / Q000209:etiology* / Q000517:prevention & control*; D018709:Statistics, Nonparametric; D013997:Time Factors
chemical_list: D000927:Anticonvulsants; D008550:Melatonin
keywords: Administration time; Effective dose; Hyperthermic febrile seizure model; Melatonin