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) and 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 maze with alleyways and doors through which the rats learn to swim to reach a platform, unlike the open pool Morris water maze task. Performance is assessed by swim time required to reach the platform and errors committed. Following initial training on maze configuration A, rats were assigned to saline, TFMPP and 8-OH-DPAT treatment groups and tested 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 error rate at any dose. Next, rats were challenged to learn new mazes following 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 learned 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 not errors, while this dose of 8-OH-DPAT markedly increased both swim time and errors. Finally, rats from all groups were tested on maze E after drug administration was discontinued, and there were no performance differences among groups. These data suggest that serotonin1A receptors may inhibit learning.