London E D, Buterbaugh G G
J Pharmacol Exp Ther. 1978 Jul;206(1):81-90.
Modification of electroshock (60 Hz; a.c.) convulsive responses and thresholds by monoamine-reducing drugs was investigated in developing rats. Throughout postnatal development, tetrabenazine (TBZ) reduced brain monoamines and increased the severity of motor responses to electroshock. The predominant maximal response in control pups progressed from hyperkinesia (day 1) to clonic convulsions (day 3) and tonic forelimb (day 7) and hindlimb (day 19) extension. The pattern in TBZ-treated pups progressed from tonic forelimb extension (day 1) to tonic hindlimb extension (day 7). On day 7, TBZ reduced the thresholds for clonic (CT) and tonic convulsions (TT) to 41 and 24% of control, respectively. Reserpine (1.25 mg/kg, 24 hours) decreased the TT but not the CT; TBZ, 4 hours before reserpine, prevented this decrease. A higher dose of reserpine (2.5 mg/kg) decreased both the CT and TT. On day 8, TBZ (25 mg/kg, 4 hours) decreased the TT (46% control); L-dihydroxyphenylalanine, but not 5-hydroxytryptophan prevented this decrease. Intracisternal 6-hydroxydopamine reduced the TT on day 8, while intracisternal 5,7-dihydroxytryptamine had no effect despite a 46% reduction in serotonin. The results indicate that in the neonatal rat brain, monoaminergic systems are sufficiently mature to attenuate electroshock convulsive responses, perhaps by limiting propagation of seizure discharge.
在发育中的大鼠中研究了单胺减少药物对电击（60赫兹；交流电）惊厥反应和阈值的影响。在整个出生后发育过程中，丁苯那嗪（TBZ）降低了脑单胺水平，并增加了对电击的运动反应的严重程度。对照幼崽中主要的最大反应从运动亢进（第1天）发展为阵挛性惊厥（第3天）以及强直性前肢（第7天）和后肢（第19天）伸展。TBZ处理的幼崽的模式从强直性前肢伸展（第1天）发展为强直性后肢伸展（第7天）。在第7天，TBZ将阵挛性惊厥（CT）和强直性惊厥（TT）的阈值分别降低至对照的41%和24%。利血平（1.25毫克/千克，24小时）降低了TT但未降低CT；在利血平给药前4小时给予TBZ可防止这种降低。更高剂量的利血平（2.5毫克/千克）降低了CT和TT两者。在第8天，TBZ（25毫克/千克，4小时）降低了TT（为对照的46%）；左旋多巴，但5-羟色氨酸不能防止这种降低。脑池内注射6-羟基多巴胺在第8天降低了TT，而脑池内注射5,7-二羟基色胺尽管血清素降低了46%但没有效果。结果表明，在新生大鼠脑中，单胺能系统已充分成熟，可通过限制癫痫放电的传播来减弱电击惊厥反应。
