EFFECTS OF DOPAMINE D-3 RECEPTOR AGONISTS ON PILOCARPINE-INDUCED LIMBIC SEIZURES IN THE RAT
EFFECTS OF DOPAMINE D-3 RECEPTOR AGONISTS ON PILOCARPINE-INDUCED LIMBIC SEIZURES IN THE RAT
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DOI：
10.1016/0306-4522(94)90281-x
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发表时间：
1994-06-01
期刊：
影响因子：
3.3
通讯作者：
STARR, MS
中科院分区：
文献类型：
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作者：
ALAM, AM;STARR, MS
离散本地化的D-3受体在核的延髓和下juvenile岛的Calleja承担了一个非常相似的多巴胺敏感的抗惊厥网站在前腹侧纹状体。为了确定这些D-3受体是否能够减弱由毛果芸香碱诱导的边缘运动性癫痫发作，在毛果芸香碱激发之前通过留置套管将具有优先或非选择性D-3亲和力的多巴胺激动剂立体定位注射到大鼠的这些边缘脑区域中。通过给予促惊厥多巴胺D-1激动剂SKF 38393（10 mg/kg i. p.）随后是亚惊厥剂量的毛果芸香碱（280-300 mg/kg i. p.）。用D-3 > D-2激动剂RU 24213（0.2 pmol-7 nmol）进行双侧内给药预处理可显著延迟癫痫发作，最小有效剂量为2 pmol，而不改变其频率或严重程度。选择性更强的D-3激动剂LY 171555（0.2 pmol-7.8 nmol）效力较低，仅在一定剂量（500 pmol）下才能减弱匹鲁卡品诱导的癫痫发作，该剂量也会刺激D-2受体。阿托伐他汀内注射高效和选择性D-3激动剂7-OH-DPAT（20 pmol至7 nmol）对匹鲁卡品诱导的癫痫发作没有保护作用。阿扑吗啡是一种混合的D-1/D-2/D-3激动剂，在100-500 pmol时延迟癫痫发作，但在更高剂量时则不然。RU 24213、LY 171555和7-OH-DPAT以D-2/D-3非选择性剂量微量注射到Calleja岛时均具有适度的抗惊厥作用，这些数据支持多巴胺系统限制癫痫发作通过边缘前脑传播的观点，但表明这种保护作用是由D-2而不是D-3受体介导的。
The discrete localization of D-3 receptors in the nucleus accumbens and subjacent islands of Calleja bears a close resemblance to the dopamine-sensitive anticonvulsant site in the anteroventral striatum. To determine if these D-3 receptors were capable of attenuating limbic motor seizures induced by pilocarpine, dopamine agonists with preferential or non-selective D-3 affinity were injected stereotaxically into these limbic brain regions of the rat via indwelling cannulae prior to pilocarpine challenge. Reliable clonic seizures were obtained by administering the proconvulsive dopamine D-1 agonist SKF 38393 (10 mg/kg i.p.) followed by a subconvulsant dose of pilocarpine (280-300 mg/kg i.p.). Bilateral intra-accumbens pretreatment with the D-3 > D-2 agonist RU 24213 (0.2 pmol-7 nmol) significantly delayed the onset of seizures, with a minimum effective dose of 2 pmol, without altering their frequency or severity. The more selective D-3 agonist LY 171555 (0.2 pmol-7.8 nmol) was less potent, and only attenuated pilocarpine-induced seizures at a dose (500 pmol that would have stimulated accumbens D-2 receptors as well. Intra-accumbens injections of the highly potent and selective D-3 agonist 7-OH-DPAT (20 pmol to 7 nmol) afforded no protection against pilocarpine-induced seizures. Apomorphine, a mixed D-1/D-2/D-3 agonist, delayed seizure onset at 100-500 pmol, but not at higher doses. RU 24213, LY 171555 and 7-OH-DPAT were all modestly anticonvulsant when microinjected into the islands of Calleja at D-2/D-3 unselective doses.These data support the notion that dopamine systems limit seizure propagation through the limbic forebrain, but suggest this protective effect is mediated by D-2 rather than D-3 receptors.