5-HT1A receptors modulate the consolidation of learning in normal and cognitively impaired rats

Attempts were made to further analyze the role of 5-HT1A receptors in conso lidation of learning by evaluating the role of these receptors in cognitive ly normal and impaired animals. The effects of post-training administration of 8-OH-DPAT and 5-HT1A receptor antagonists, WAY 100135, WAY 100635, and S-UH-301, plus the cholinergic and glutamatergic antagonists, scopolamine a nd dizolcipine, respectively, were determined using an autoshaping learning task. The results showed that 8-OH-DPAT increased the number of conditione d responses, whereas WAY100135, WAY100635, and S-UH-301, and the 5-HT deple ter, p-chloroamphetamine (PCA), had no effect. PCA did not change the silen t properties of the 5-MT1A receptor antagonists. PCA, WAY100635, and S-UH-3 01, but not GR127935 (a 5-HT1B/1D-receptor antagonist) or MDL100907 (a 5-MT 2A receptor antagonist), reversed the effect to 8-OH-DPAT. Ketanserin (a 5- MT2A/2C receptor antagonist) and ondansetron (a 5-MT3 receptor antagonist), at a dose that increased the conditioned responses by itself, reversed the effect of 8-OH-DPAT. Moreover, 8-OH-DPAT or S-UH-301 reversed the learning deficit induced by scopolamine and dizocilpine whereas WAY100635 reversed the effect of scopolamine only. These data confirm a role for presynaptic 5 -MT1A receptors during the consolidation of learning and support the hypoth esis that serotonergic, cholinergic, and glutamatergic systems interact in cognitively impaired animals. (C) 1999 Academic Press.