Meneses A, Terrón J A
Departamento de Farmacobiología, CINVESTAV-IPN, AP 22026, 14000 Mexico City, Mexico.
Behav Brain Res. 2001 Jun;121(1-2):21-8. doi: 10.1016/s0166-4328(00)00378-8.
The present study further explored the mechanisms involved in the facilitatory effect induced by (+/-)-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on learning consolidation. For this purpose, we analyzed in parallel the effects of LY215840 and ritanserin, two 5-HT(2) receptor antagonists with high affinity for the 5-HT(7) receptor, and WAY100635, a selective 5-HT(1A) receptor antagonist, on the facilitatory effect induced by 8-OH-DPAT on learning consolidation. We also determined whether LY215840 and/or ritanserin could be beneficial in restoring a deficient learning condition. Using the model of autoshaping task, post-training injection of LY215840 or WAY100635 had no effect on learning consolidation. However, both drugs abolished the enhancing effect of 8-OH-DPAT, with LY215840 being slightly more effective than WAY100635 in this respect. Ritanserin produced an increase in performance by itself and also abolished the effect of 8-OH-DPAT. Remarkably, selective blockade of 5-HT(2A) and 5-HT(2B/2C) receptors with MDL100907 and SB200646, respectively, failed to alter the 8-OH-DPAT effect. LY215840 and ritanserin, at the doses that inhibited the 8-OH-DPAT-induced response, reversed the learning deficits induced by scopolamine and dizocilpine. The present results suggest that the enhancing effect produced by 8-OH-DPAT on learning consolidation involves activation of 5-HT(1A) receptors and an additional mechanism, probably related to the 5-HT(7) receptor. Blockade of 5-HT(2) receptors, and perhaps of 5-HT(7) receptors as well, may provide some benefit in reversing learning deficits associated with decreased cholinergic and/or glutamatergic neurotransmission.
本研究进一步探讨了（±）-8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）诱导的促进学习巩固作用的相关机制。为此，我们同时分析了LY215840和利坦色林（两种对5-HT₇受体具有高亲和力的5-HT₂受体拮抗剂）以及WAY100635（一种选择性5-HT₁A受体拮抗剂）对8-OH-DPAT诱导的学习巩固促进作用的影响。我们还确定了LY215840和/或利坦色林是否有助于恢复学习缺陷状态。使用自动成型任务模型，训练后注射LY215840或WAY100635对学习巩固没有影响。然而，两种药物都消除了8-OH-DPAT的增强作用，在这方面LY215840比WAY100635稍有效。利坦色林本身提高了表现，也消除了8-OH-DPAT的作用。值得注意的是，分别用MDL100907和SB200646选择性阻断5-HT₂A和5-HT₂B/₂C受体未能改变8-OH-DPAT的作用。LY215840和利坦色林在抑制8-OH-DPAT诱导反应的剂量下，逆转了东莨菪碱和地佐环平诱导的学习缺陷。目前的结果表明，8-OH-DPAT对学习巩固产生的增强作用涉及5-HT₁A受体的激活以及另一种可能与5-HT₇受体相关的机制。阻断5-HT₂受体，或许还有5-HT₇受体，可能在逆转与胆碱能和/或谷氨酸能神经传递减少相关的学习缺陷方面提供一些益处。
