Working memory deficits induced by single but not repeated exposures to domoic acid.

Single injections of domoic acid, given either intraperitoneally to mice or directly into the hippocampal formation of rats, have been shown to impair learning on the place version of the Morris water maze task and the eight arm radial maze task. The present study was designed to test whether both single and repeated exposures of intraperitoneally administered domoic acid (1.0 or 2.0 mg/kg) impair spatial working memory in mice on a delayed matching-to-sample task. DBA strain mice were given a series of four injections over a 7-day period consisting of either saline or one of two doses of domoic acid. During the 18 days of testing, each subject was given one trial per day consisting of one information run, followed by three test runs. On non-alternation days (days in which the correct response was the same as the preceding day) the saline injected group significantly outperformed the single injection 2.0 mg/kg domoic acid group. This indicates that domoic acid-treated animals were incapable of forming a memory that persisted for 24 h and hence were less able to utilize the prior day's experience. However, the repeated exposure groups did not perform as poorly on non-alternation days than the single exposure groups, indicating that domoic acid may affect multiple mechanisms involved in memory consolidation.