8‐Hydroxy‐2‐(di‐n‐propylamino)tetralin impairs spatial learning in a water maze: role of postsynaptic 5‐HT1A receptors

Abstract

The effect of 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OH‐DPAT), a 5‐HT1A receptor agonist, on place navigation was studied by use of two spatial tasks in a water maze. In the first experiment, rats treated subcutaneously with 100 and 300 (but not 30) μg kg−1 8‐OH‐DPAT were impaired in their ability to locate a hidden platform. The probe test confirmed the impairment of spatial navigation but the effect (time spent in the training quadrant) was quantitatively different, depending on whether 8‐OH‐DPAT was administered only before each training session, only before the probe test or in both conditions. In the second experiment, rats received 150 μg 5,7‐dihydroxytryptamine (5,7‐DHT) intracerebroventricularly to destroy 5‐hydroxytryptamine (5‐HT)‐containing neurones and 24 days later were examined for choice accuracy in a two‐platform spatial discrimination task. At 100 (but not 30) μg kg−1 8‐OH‐DPAT impaired rats' accuracy with no effect on latency and no errors of omission. In 5,7‐DHT‐treated rats, this dose had a greater effect, including errors of omission. Sham‐operated rats injected with 300 μg kg−1 8‐OH‐DPAT were markedly impaired in accuracy but they had longer latencies and made more errors than controls. All the effects were increased in 5,7‐DHT treated rats. The results suggest that, at doses causing no apparent changes in motor behaviour or motivation, 8‐OH‐DPAT impairs spatial navigation by stimulating postsynaptic 5‐HT1A receptors in the rat brain. 1992 British Pharmacological Society