EFFECTS OF THE 5-HT RECEPTOR ANTAGONISTS GR127935 (5-HT1B 1D) AND MDL100907 (5-HT2A) IN THE CONSOLIDATION OF LEARNING/

We have previously reported that 5-HT1B/1D and 5-HT2A/2B/2C receptors play a role in learning and memory. The present investigation was devo ted to analyze further in the autoshaping learning task: (I) the effec ts of the 5-HT1A/1B/1D receptor agonist, GR46611, the 5-HT1B/1D recept or antagonist, GR127935, and the selective 5-HT2A receptor antagonist, MDL100907. Consistent with a role of 5-HT1B/1D receptors in learning, the post-training injection of GR46611 (1-10 mg/kg) decreased the con solidation of learning whereas GR127935 (10 mg/kg) increased it; the e ffects of both drugs were reversed by PCA pretreatment. GR127935 aboli shed the decrease induced by GR46611, TFMPP and mCPP, whereas MDL10090 7 (0.1-3.0 mg/kg) had no effect by itself but abolished the effects of DOI, ketanserin and TFMPP and moderately inhibited the effects elicit ed by mCPP, I-NP and mesulergine. Neither did GR127935 nor MDL100907 s ignificantly modify the increase in the consolidation of learning indu ced by 8-OH-DPAT. Thus, the present findings suggest that stimulation of presynaptic 5-HT1B/1D receptors impairs the consolidation of learni ng whilst stimulation of 5-HT2A/2C receptors enhances it; the blockade of 5-HT2A receptors has no effects. In addition, 5-HT2 receptors seem to modulate this cognitive stage. (C) 1997 Elsevier Science B.V.