Engelbrecht A H, Russell V A, Mintz M, Lamm M C, Kellaway L, Herberg L J, Taljaard J J
Department of Chemical Pathology, University of Stellenbosch, Tygerberg Hospital, South Africa.
Pharmacol Biochem Behav. 1996 Nov;55(3):315-21. doi: 10.1016/s0091-3057(96)00099-8.
Epileptic seizures are thought to terminate largely as a result of the extracellular accumulation of the purinergic neuromodulator, adenosine, released by discharging neurons. However, the postictal surge in extracellular adenosine and its widespread inhibitory effects are limited in time to only a few minutes and cannot directly account for increased resistance to seizures and the complex behavioural and motivational effects that may persist for hours or days after a seizure. The present study examined whether kindled seizures might alter the sensitivity or efficacy of inhibitory presynaptic adenosine receptors, and thereby induce more enduring changes in downstream transmitter systems. Rats were kindled in the amygdala of the dominant cerebral hemisphere, contralateral to the preferred direction of rotation, and their brains were removed either 2 h or 28 days after completion of kindling. Inhibition of electrically stimulated release of dopamine (DA) and acetylcholine (ACh) by the A1 adenosine-receptor agonist, R-phenylisopropyladenosine (R-PIA) was then measured in the prefrontal cortex (PFC) and nucleus accumbens. R-PIA (1.0 microM) inhibited [1H]DA release from PFC and nucleus accumbens tissue, and [14C]ACh release from nucleus accumbens tissue, but release was unaffected by prior kindling, regardless of the intervening interval. These results do not support suggestions that DA or ACh might mediate the effects of seizure-induced changes in purinergic inhibitory tone so as to cause long-term shifts in seizure threshold and postictal behavior.
癫痫发作被认为主要是由于放电神经元释放的嘌呤能神经调质腺苷在细胞外积累而终止。然而，发作后细胞外腺苷的激增及其广泛的抑制作用在时间上仅局限于几分钟，无法直接解释对癫痫发作抵抗力的增加以及可能在发作后持续数小时或数天的复杂行为和动机效应。本研究探讨点燃性癫痫发作是否可能改变抑制性突触前腺苷受体的敏感性或效能，从而在下游递质系统中诱导更持久的变化。将大鼠在优势大脑半球杏仁核中点燃，该半球与首选旋转方向对侧，在点燃完成后2小时或28天取出它们的大脑。然后在前额叶皮质（PFC）和伏隔核中测量A1腺苷受体激动剂R-苯异丙基腺苷（R-PIA）对电刺激释放多巴胺（DA）和乙酰胆碱（ACh）的抑制作用。R-PIA（1.0微摩尔）抑制PFC和伏隔核组织中[1H]DA的释放以及伏隔核组织中[14C]ACh的释放，但无论中间间隔如何，释放均不受先前点燃的影响。这些结果不支持DA或ACh可能介导癫痫发作诱导的嘌呤能抑制性张力变化的作用，从而导致癫痫发作阈值和发作后行为的长期改变的观点。
