Rosen J B, Weiss S R, Post R M
Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, MD 20892.
Brain Res. 1994 Jul 18;651(1-2):252-60. doi: 10.1016/0006-8993(94)90704-8.
Tolerance to carbamazepine's anticonvulsant effects on amygdala kindled seizures occurs contingently, that is, only when carbamazepine is given prior to, but not after the seizure occurs. Biological correlates of contingent tolerance were examined using in situ hybridization and receptor binding techniques for thyrotropin-releasing hormone (TRH) mRNA and TRH receptor binding. Rats were fully kindled and given daily injections of carbamazepine (15 mg/kg, i.p.) either 15 min before (CBZ-before) or after (CBZ-after) amygdala stimulation until the CBZ-before rats became tolerant. Kindled rats were matched so that the two groups had an equal number of seizures and doses of CBZ. Three other groups were also used for comparison: kindled rats that received vehicle injections, and sham-kindled animals treated with either vehicle or CBZ. Rats were sacrificed 4 h after the last seizure or sham stimulation. Both sham-kindled rat groups had barely detectable levels of TRH mRNA. In the CBZ-after (non-tolerant) and vehicle-kindled rats, TRH mRNA levels were increased in the dentate gyrus, pyriform, entorhinal, and perirhinal cortices. In contrast to the other kindled animals, the CBZ-before rats (tolerant) had dramatically diminished TRH mRNA levels bilaterally in the dentate gyrus and pyriform cortex, and ipsilateral to the stimulation in the entorhinal cortex. Decreases in TRH receptor binding were demonstrated autoradiographically in the dentate gyrus and perirhinal cortex in all of the kindled groups with no differences between tolerant and non-tolerant rats.(ABSTRACT TRUNCATED AT 250 WORDS)
对卡马西平抗惊厥作用于杏仁核点燃癫痫发作的耐受性是偶然发生的，也就是说，只有当卡马西平在癫痫发作之前而非之后给药时才会出现。使用促甲状腺激素释放激素（TRH）mRNA原位杂交和受体结合技术研究了偶然耐受性的生物学相关性。将大鼠完全点燃，每天在杏仁核刺激前15分钟（卡马西平-之前组）或之后（卡马西平-之后组）腹腔注射卡马西平（15mg/kg），直到卡马西平-之前组的大鼠产生耐受性。将点燃的大鼠进行匹配，使两组癫痫发作次数和卡马西平剂量相等。另外三组也用于比较：接受溶剂注射的点燃大鼠，以及接受溶剂或卡马西平治疗的假点燃动物。在最后一次癫痫发作或假刺激后4小时处死大鼠。两个假点燃大鼠组的TRH mRNA水平几乎检测不到。在卡马西平-之后组（非耐受组）和溶剂-点燃大鼠中，齿状回、梨状皮质、内嗅皮质和鼻周皮质的TRH mRNA水平升高。与其他点燃动物相比，卡马西平-之前组的大鼠（耐受组）在齿状回和梨状皮质双侧以及内嗅皮质刺激同侧的TRH mRNA水平显著降低。在所有点燃组的齿状回和鼻周皮质中，通过放射自显影证明TRH受体结合减少，耐受和非耐受大鼠之间没有差异。（摘要截断于250字）
