EFFECTS OF THE SEROTONIN RECEPTOR AGONISTS 8-OH-DPAT AND TFMPP ON LEARNING AS ASSESSED USING A NOVEL WATER MAZE

We evaluated the effects of two drugs active at serotonin receptors, 8 -hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, a 5-HT1A agonist) an d N-3-trifluoromethylphenyl)piperazine hydrochloride (TFMPP, a 5-HT2C agonist) on learning using a novel water maze previously characterized in our laboratory. The water maze utilized is a traditional type of m aze with alleyways and doors through which the rats learn to swim to r each a platform, unlike the open pool Morris water maze task. Performa nce is assessed by swim time required to reach the platform and errors committed. Following initial training on maze configuration A, rats w ere assigned to saline, TFMPP and 8-OH-DPAT treatment groups and teste d for performance once per dose, 30 min after administration of drug ( 0.25. 0.5, and 1.0 mg/kg IP). Swim times were significantly increased as compared to saline for all doses for both drugs. The error rate was increased for 8-OH-DPAT at all doses, while TFMPP had no effect on er ror rate at any dose. Next, rats were challenged to learn new mazes fo llowing daily administration of 0.25 or 0.5 mg/kg of each drug 30 min prior to each daily swim trial. Rats given 0.25 mg/kg of 8-OH-DPAT lea rned new maze C more slowly than saline-treated rats, while TFMPP had no effect at this dose. At the higher dose of 0.5 mg/kg, tested on new maze B, TFMPP administration significantly increased swim times but n ot errors, while this dose of 8-OH-DPAT markedly increased both swim t ime and errors. Finally, rats from all groups were tested on maze E af ter drug administration was discontinued, and there were no performanc e differences among groups. These data suggest that serotonin(1A) rece ptors may inhibit learning.