5-HT1A receptor agonist (8-OH-DPAT) and 5-HT2 receptor agonist (DOI) disrupt the non-cognitive performance of rats in a working memory task

The present study investigated the role of 5-HT1A and 5-HT2 receptors in the execution of a working memory task (delayed non-matching to position, DNMTP) by assessing the influence of 8-OH-DPAT (5-HT1A receptor agonist) and DOI (5-HT2 receptor agonist) on the performance of rats lesioned with 5,7-dihydroxytryptamine (5,7-DHT) and their controls. Post-mortem neurochemical analysis revealed that serotonin and 5-hydroxyindoleacetic acid levels were reduced in examined brain areas (especially in the hippocampus where there was a 90 percent reduction). Noradrenaline concentrations were also decreased (mostly on the same side of the injection) by about 20 percent. 5,7-DHT lesioned rats did not significantly differ from their controls in performance in the DNMTP task. At the 30 mu g/kg dose, 8-OH-DPAT did not affect the DNMTP-performance of rats, but at the higher dose (100 mu g/kg) it reduced the probability of responding to the sample lever, DOI (100 and 300 mu g/kg) also interfered with the non-cognitive performance of rats. Since neither of these agonists affected significantly the choice accuracy, they do not appear to influence the working memory per se. The 5,7-DHT lesioned rats did not differ from their controls in response to these agonists. These results suggest that the combination of 5-HT1A receptor stimulation by 8-OH-DPAT and 5-HT2 receptor stimulation by DOI can interfere with the non-cognitive performance of rats in the DNMTP task. The results further indicate that the effect of 8-OH-DPAT may be mediated through post-synaptic rather than pre-synaptic 5-HT1A receptors.