Objective To observe the impact of zotepine on the excitatory synaptic response and long term potentiation (LTP) of dentate gyrus neurons.Methods Male rabbits ( n = 20) weighting about 2.5 ～ 3.5 kg were divided into four groups randomly ( n = 5 ): control, zotepine 1.0, zotepine 2.0 and zotepine 5.0.To each rabbit,there were 60 results during 120 min.Population spike(PS) amplitude and excitory postsynaptic potential (EPSP) slope were used to be the indexes of the excitatory synaptic response of dentate gyrus neurons.The sequence was base response ( at the beginning), intraperitoneal injection of 0.5ml dimethylsulfoxide or 0.5ml zotepine-dimethylsulfoxide solution ( 1.0,2.0,5.0 mg/kg of zotepine dosage) ( after 30 min) and titanic stimulation (after 90 min).Results To 4 groups,the PS amplitude and EPSP slope after single stimuli were not significantly different from those before single stimuli.In control group, the PS amplitude and EPSP slope after titanic stimulation[(0.68 ± 0.052)mV and(0.633 ± 0.024 )mV/ms] were significantly different from those before injection[(0.266 ±0.008) mV and(0.246 ±0.010) mV/ms] (P＜0.05 ～0.01 ) ,and LTP were induced.LTP were not induced after titanic stimulation in group zotepine 1.0,2.0 and 5.0.After titanic stimulation, the PS amplitude and EPSP slope in group zotepine 5.0[(0.277 ±0.008)mV and(0.296 ±0.007) mV/ms] were significantly different from those in group control(P＜ 0.05).Conclusion Zotepine had little effect on the excitatory synaptic response of dentate gyrus neurons after single stimuli in perforant path, while it blocked the induction of LTP in perforant path-dentate gyrus pathway.

BACKGROUND AND PURPOSE: Migraine patients are particularly prone to the complication of medication-overuse headache (MOH). Although it has been shown that A allele carriers for the tumor necrosis factor (TNF)-beta gene G252A polymorphism are at high risk of the development of migraine without aura, the relationship between the TNF-beta gene G252A polymorphism and MOH is unknown. We investigated whether the TNF-beta gene G252A polymorphism is involved in the aggravation of migraine by overuse of medications. METHODS: Forty-seven migraine patients (6 males and 41 females; age 36.4+/-10.3 years, mean+/-SD) and 22 MOH patients (1 male and 21 females; age 39.6+/-9.9 years) who had migraine were included in this study. The genotype for the TNF-beta gene G252A polymorphism was determined by polymerase-chain-reaction restriction-fragment-length polymorphism analysis. RESULTS: The distribution of TNF-beta gene G252A genotype frequency differed significantly between migraine and MOH patients (p=0.013). The G/G genotype was carried by 23% of the migraine patients but it was absent in MOH patients. CONCLUSIONS: G/G genotype carriers appear to be less susceptible to the aggravation of migraine by overuse of medications. The G252A TNF-beta gene polymorphism may be one of the factors contributing to the complications of MOH in patients with migraine.
Alleles ; Genotype ; Headache ; Humans ; Lymphotoxin-alpha ; Male ; Migraine Disorders ; Migraine without Aura ; Tumor Necrosis Factor-alpha