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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

A.I. Virtanen Institute

Ewen MacDonald

Department of Pharmacology and Toxicology, University of Kuopio, P.O.Box 1627 FIN-70211 Kuopio

Esa Koivisto

Department of Neuroscience and Neurology

Roman Stefanski

Department of Neuroscience and Neurology

Antti Haapalinna

Orion Corporation, R&D Pharmaceuticals, P.O.Box 425 FIN-20101, Turku, Finland

Paavo Riekkinen, JR

Department of Neuroscience and Neurology, Department of Neurology, Kuopio University Hospital

Jouni Sirviö

A.I. Virtanen Institute

The present study investigated the role of 5-HT_1A 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-HT_1A receptor agonist) and DOI (5-HT ₂ 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 µg/kg dose, 8-OH-DPAT did not affect the DNMTP-performance of rats, but at the higher dose (100 µg/kg) it reduced the probability of responding to the sample lever. DOI (100 and 300 µg/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-HT_1A 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-HT_1A receptors.

Key Words: 5,7-DHT • DOI • 8-OH-DPAT • rat • serotonin receptor • working memory

Journal of Psychopharmacology, Vol. 12, No. 2, 177-185 (1998)
DOI: 10.1177/026988119801200210


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