SR141716A antagonizes the disruptive effects of cannabinoid ligands on learning in rats.
SR141716A antagonizes the disruptive effects of cannabinoid ligands on learning in rats.
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发表时间：
1997-09
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通讯作者：
J. Brodkin;J. M. Moerschbaecher
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作者：
J. Brodkin;J. M. Moerschbaecher
研究了大麻素配体对重复获取过程中反应的大鼠的影响。每组大鼠被要求学习一个不同的三反应序列；每正确完成序列的三分之一，就会出现一个食物颗粒。错误产生了短暂的超时，但没有重置链。注射中枢不活跃的大麻素大麻二醇(3.2-100 mg/kg i.p.)和内源性配体anandamide(0.01-18 mg/kg i.p.)都不影响反应的速度或准确性。相比之下，Delta9-四氢大麻酚(3.2-18 mg/kg i.p.)而内源性配体的长效类似物R-甲烷胺(1-18 mg/kg ip)可引起总错误百分比的剂量相关增加和应答率的下降。脑大麻素受体拮抗剂SR141716A(1-32 mg/kg)单独给药时，既不影响准确性，也不影响反应速度。低剂量的SR141716A(1毫克/公斤)单独给药没有影响，可拮抗Delta9-四氢大麻酚和R-甲烷酰胺对反应速度和准确性的干扰效应，并使剂量-效应曲线估计右移3倍。然而，给予SR141716A并不改变吗啡的作用。这些结果表明，大麻素激动剂通过刺激大麻素受体而导致大鼠学习障碍。数据进一步表明，虽然类似大麻的药物可以扰乱学习，但厌胺系统可能并不参与学习。
The effects of cannabinoid ligands were studied in rats responding under a repeated acquisition procedure. Each session rats were required to learn a different three-response sequence; every third correct completion of the sequence resulted in the presentation of a food pellet. Errors produced a brief timeout but did not reset the chain. Neither injections of the centrally inactive cannabinoid, cannabidiol (3.2-100 mg/kg i.p.), nor the endogenous ligand, anandamide (0.01-18 mg/kg i.p.), affected rate or accuracy of responding. In contrast, delta9-tetrahydrocannabinol (3.2-18 mg/kg i.p.) and the long-acting analog of the endogenous ligand, R-methanandamide (1-18 mg/kg i.p.), produced dose-related increases in the total percentage of errors and decreases in the rate of responding. The brain cannabinoid receptor antagonist SR141716A (1-32 mg/ kg) did not affect either accuracy or rate of responding when administered alone. A low dose of SR141716A (1 mg/kg), which had no effect when administered alone, antagonized the disruptive effects of delta9-tetrahydrocannabinol and R-methanandamide on rate and accuracy of responding and produced an estimated 3-fold shift to the right in the dose-effect curves. However, administration of SR141716A did not alter the effects of morphine. These results suggest that cannabinoid agonists produce disruptions of learning in rats through stimulation of the cannabinoid receptor. The data further suggest that whereas cannabimimetic agents can disrupt learning, the anandaminergic system may not be tonically involved in learning.