Andrade Chittaranjan, Thyagarajan Shivashanmugam, Singh Nagendra Madan, Vinod Pabbisetty S, Sanjay Kumar Rao N, Chandra J Suresh
Department of Psychopharmacology, National Institute of Mental Health and Neurosciences, Bangalore 560 029, India.
J Neural Transm (Vienna). 2008 Jul;115(7):1063-70. doi: 10.1007/s00702-008-0063-2. Epub 2008 Jun 4.
Cyclooxygenase-2 (COX-2) mechanisms are involved in glutamate-mediated learning and memory as well as in glutamatergic excitotoxicity. Electroconvulsive therapy (ECT)-induced amnesia may arise from glutamatergic excitotoxicity; if so, COX-2 inhibition may attenuate retrograde amnesia with ECT.
Wistar rats which received celecoxib (15 mg/kg per day) or vehicle for 18 days were trained for 3 days on a passive avoidance task. On each of the next 3 days, rats which showed perfect learning (n=51) received true or sham suprathreshold electroconvulsive shocks (ECS; 60 mC) in a factorial design; daily dosing with drug or vehicle was continued. One day after the last ECS, recall of pre-ECS learning was tested.
ECS-treated rats showed impaired recall in the vehicle but not celecoxib group. Celecoxib significantly protected against ECS-induced retrograde amnesia; this benefit was independent of the drug-induced attenuation of ECS seizure duration.
Celecoxib may protect against ECS-induced retrograde amnesia by attenuating ECS-induced, COX-2-mediated glutamatergic excitotoxicity.
环氧化酶-2（COX-2）机制参与谷氨酸介导的学习和记忆以及谷氨酸能兴奋性毒性。电惊厥治疗（ECT）诱导的失忆可能源于谷氨酸能兴奋性毒性；如果是这样，COX-2抑制可能会减轻ECT引起的逆行性失忆。
将接受塞来昔布（每天15毫克/千克）或赋形剂治疗18天的Wistar大鼠在被动回避任务上训练3天。在接下来的3天里，每天对表现出完美学习能力的大鼠（n = 51）进行真或假的阈上电惊厥刺激（ECS；60毫库仑），采用析因设计；继续每日给予药物或赋形剂。在最后一次ECS刺激后一天，测试对ECS刺激前学习的记忆。
接受ECS刺激的大鼠在给予赋形剂组中表现出记忆受损，但在塞来昔布组中未出现。塞来昔布显著预防了ECS诱导的逆行性失忆；这种益处与药物诱导的ECS发作持续时间缩短无关。
塞来昔布可能通过减轻ECS诱导的、COX-2介导的谷氨酸能兴奋性毒性来预防ECS诱导的逆行性失忆。
