Role of 5-HT1A and 5-HT7 receptors in the facilitatory response induced by 8-OH-DPAT on learning consolidation

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 LY215830 and ritanserin, two 5-HT2 receptor antagonists with high affinity for the 5-HT7 receptor, and WAY100635, a selective 5-HT1A 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 LY215810 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-HT2A and 5-HT2B-2C receptors with MDL100907 and SB200646, respectively, railed 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-HT1A receptors and an additional mechanism, probably related to the 5-HT7 receptor. Blockade of 5-HT2 receptors, and perhaps of 5-HT7 receptors as well, may provide some benefit in reversing learning deficits associated with decreased cholinergic and/or glutamatergic neurotransmission. (C) 2001 Elsevier Science B.V. All rights reserved.