Getova D, Bowery N G, Spassov V
Department of Pharmacology, Medical School, University of Birmingham, UK.
Eur J Pharmacol. 1997 Feb 5;320(1):9-13. doi: 10.1016/s0014-2999(96)00877-1.
A variety of animal models of absence epilepsy have been described and among these exists a genetically susceptible strain of rat (genetic absence epilepsy rats of Strasbourg (GAERS)). These rats produce periods of behavioural arrest with simultaneous production of cortical spike and wave discharges (SWD). GABAB receptor antagonists suppress completely the production of these spike and wave discharges. GABAB receptor ligands have also been reported to affect cognitive performance in rodents. The present study examined the cognitive performance of GAERS and the influence of GABAB receptor antagonists on this activity. Rats were injected intraperitoneally once per day with saline or a GABAB receptor antagonist (CGP 36742 (3-amino-propyl-n-butyl-phosphinic acid) 100 mg/kg; CGP 56433 ([3-(1-(S)-[(3-(cyclohexylmethyl)hydroxy phosphinyl]-2-(S) hydroxy propyl] amino]ethyl]benzoic acid) ([3-{1-(S)-[{3-(cyclohexylmethyl)hydroxy phosphinyl]-2-(S) hydroxy propyl] amino]ethyl]benzoic acid) 1 mg/kg or CGP 61334 ([3-({[3-[(diethoxymethyl)hydroxy phosphinyl]propyl] amino}methyl]-benzoic acid (1 mg/kg). A two-way active avoidance test paradigm with negative reinforcement was used. Untreated GAERS performed significantly better than non-epileptic rats (P < 0.05) and this enhancement in cognitive performance was sustained in rats treated with the GABAB receptor antagonists.
已经描述了多种失神癫痫的动物模型，其中存在一种对癫痫遗传易感的大鼠品系（斯特拉斯堡遗传性失神癫痫大鼠（GAERS））。这些大鼠会出现行为停滞期，同时产生皮质棘波和慢波放电（SWD）。GABAB受体拮抗剂可完全抑制这些棘波和慢波放电的产生。据报道，GABAB受体配体也会影响啮齿动物的认知能力。本研究检测了GAERS的认知能力以及GABAB受体拮抗剂对该能力的影响。大鼠每天腹腔注射一次生理盐水或一种GABAB受体拮抗剂（CGP 36742（3-氨基丙基-n-丁基次膦酸）100毫克/千克；CGP 56433（[3-(1-(S)-[(3-(环己基甲基)羟基膦酰基]-2-(S)-羟基丙基]氨基]乙基]苯甲酸）1毫克/千克或CGP 61334（[3-({[3-[(二乙氧基甲基)羟基膦酰基]丙基]氨基}甲基]-苯甲酸）（1毫克/千克）。采用具有负强化的双向主动回避试验范式。未经治疗的GAERS表现显著优于非癫痫大鼠（P<0.05），并且在用GABAB受体拮抗剂治疗的大鼠中，这种认知能力的增强得以维持。
