EFFECTS OF THE SEROTONIN AGONISTS 8-OH-DPAT, BUSPIRONE, AND DOI ON WATER MAZE PERFORMANCE

We have previously reported that the serotonin 5-HT1A agonist 8-OH-DPA T and the 5-HT2C agonist TFMPP impair performance on a water maze. In the present report we extended those studies by examining a second 5-H T1A agonist, buspirone, to see whether its effects paralleled those of 8-OH-DPAT, and by testing the effects of the 5-HT2 agonist DOI. Unlik e the open pool Morris water maze, the maze used in these experiments has alleys and doorways. The maze can be easily reconfigured to presen t rats with both previously learned or new maze challenges. Performanc e is assessed by time to reach the maze exit platform and the number o f wrong doorways entered (errors). At doses that did not affect perfor mance in a previously learned maze, the 5-HT1A agonists 8-OH-DPAT (0.1 mg/kg) and buspirone (1 mg/kg) slowed acquisition of a new maze confi guration as measured by both swim time to the exit platform and errors committed. A higher dose of buspirone (10 mg/kg) completely blocked a cquisition of a novel maze. In contrast, DOI slowed performance as ass essed by swim time on both a well-learned maze as well as acqui sition of a new maze, but did not affect error rate on either task, suggesti ng that this 5-HT2 agonist impaired performance by depressing motor ac tivity. These experiments demonstrate that serotonin agonists, especia lly the 5-HT1A subtype, can impair learning. (C) 1998 Elsevier Science Inc.