腺苷A_(2A)受体阻断剂SCH58261对大鼠杏仁核点燃癫痫模型的影响

Protective effect of adenosine A_(2A) receptor antagonist SCH58261 on amygdalakindled seizures in Wistovr rats

目的研究腺苷A2A受体阻断剂SCH58261对大鼠杏仁核点燃癫痫模型的作用。方法制作杏仁核电刺激模型。点燃成功后的大鼠,通过腹腔给药的方法,观察SCH58261对模型成功后各发作参数的作用。整个实验过程中,严密观察药物对大鼠行为学的影响。结果在成功点燃的癫痫模型中,SCH58261(0.005,0.05,0.5mg/kg)对全面性发作阈值(GST)没有影响。以GST(+4μA)为刺激强度,SCH58261(0.005,0.05mg/kg)可以降低杏仁核后放电时间(ADD),运动性发作持续时间(MSD),5级发作持续时间(S5D)和癫痫发作总的持续时间(SD);SCH58261(0.005,0.05mg/kg)对癫痫4级发作潜伏期(S4L)和癫痫发作状态(SS)没有影响;SCH58261(0.5mg/kg)对点燃模型各发作参数均无抑制作用。以2×GST为刺激强度,SCH58261(0.05mg/kg)对ADD和S5D均无明显抑制作用,但可以降低MSD和SD发作时间。结论 SCH58261在0.005-0.05mg/kg范围内可以抑制模型点燃成功后痫性发作。

Objective Evaluate the effect of adenosine A2 Areceptor antagonist SCH58261 on amygdala-kindled seizures and its potential for epileptogenesis.Methods Kindling was accomplished through stimulitingthe amygdala in rats.Then effect of SCH58261 was studied in fully kindled rats after intraperitoneal injection.In addition,In all experiments,behavioral changes in the rats in response to SCH58261 were monitored closely.Results In fully amygdala-kindled rats SCH58261（0.005,0.05,0.5mg/kg）had no effect on generalized seizure threshold（GST）.In the stimulus intensity of GST（＋4μA）SCH58261（0.005,0.05mg/kg）decreased afterdischage duration（ADD）,motor seizure duration（MSD）,stage 5duration（S5D）and seizure duration（SD）;it had no influence on stage 4latency（S4L）and seizure stage（SS）.SCH58261（0.5 mg/kg）had no effect on all seizure parameters.In the stimulus intensity of 2×GST SCH58261（0.05mg/kg）decreased MSD and SD,but can not affect ADD and S5 D.Conclusion SCH58261 had potent anticonvulsant profile and little adverse effects at the dosage of 0.005-0.05mg/kg,suggesting that the substance was effective against amygdala-kindled seizures.