8-Hydroxy-2-(di-n-propylamino)tetralin impairs spatial learning in a water maze: role of postsynaptic 5-HT1A receptors.
1. The effects 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. 2. In the first experiment, rats treated subcutaneously with 100 and 300 (but not 30) micrograms 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. 3. In the second experiment, rats received 150 micrograms 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. 4. At 100 (but not 30) micrograms 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 micrograms 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. 5. 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.
Carli
M
M
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Samanin
R
R
D015116:5,7-Dihydroxytryptamine / Q000008:administration & dosage / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D013028:Space Perception / Q000187:drug effects*; D013550:Swimming; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin