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 microg/kg dose, 8-OH-DPAT did not affect the DNMTP-performance of rats, but at the higher dose (100 microg/kg) it reduced the probability of responding to the sample lever. DOI (100 and 300 microg/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.
Ruotsalainen
S
S
A.I. Virtanen Institute, Kuopio University Hospital, Finland. Sirja.Ruotsalainen@uku.fi
MacDonald
E
E
Koivisto
E
E
Stefanski
R
R
Haapalinna
A
A
Riekkinen
P
P
Sirviö
J
J
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D011939:Mental Recall / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000662:Amphetamines; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017366:Serotonin Receptor Agonists; D006897:Hydroxyindoleacetic Acid; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D009638:Norepinephrine