Effects of rolipram on scopolamine-induced impairment of working and reference memory in the radial-arm maze tests in rats

Rationale: Rolipram, a selective inhibitor of cyclic AMP-specific phosphodiesterase (PDE4), has been shown to enhance scopolamine-induced impair- ment of working memory. However, its effect on refer- ence memory, which appears to be related to the level of cyclic AMP (cAMP), has not been investigated yet; in addition, the mechanism involved in its effects on mem- ory remains to be elucidated. Objectives: To investigate the effects of rolipram on working and reference memo- ries impaired by scopolamine and the involvement of cAMP. Methods: By administration (IP) of rolipram and forskolin, an activator of adenylyl cyclase (AC), the ef- fects of both drugs on the number of correct choices and errors in experiment 1 and, the frequency of both work- ing memory errors and reference memory errors in experiment 2 were observed in two eight-arm radial maze tasks in rats. Results: In experiment 1, rolipram (0.01-1.0 mg/kg) attenuated the scopolamine-induced (0.5 mg/kg) increase in the total number of errors in dose- and time-dependent manners. The minimum effec- tive dose of rolipram was 0.05 mg/kg and the effects lasted nearly 60 min. By contrast, forskolin (1.0- 10.0 mg/kg) failed significantly to affect any of the above indices altered by scopolamine. In experiment 2, rolipram (0.05 and 0.1 mg/kg) decreased the frequencies of both working and reference memory errors that were elevated by scopolamine. Forskolin did not alter either type of error at a dose that increased the exploration time. Conclusion: Rolipram may exert its effects of re- versing both working and reference memory impair- ments via increased cyclic AMP concentrations in cer- tain signal transduction pathways, rather than by a gener- alized increase in cAMP.