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Psychopharmacology (Berl). 2000 Jun;150(3):311-6.

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

Author information

1
Department of Pharmacology and Therapeutics, Louisiana State University Medical Center, Shreveport 71130, USA. hzhang@lsumc.edu

Abstract

RATIONALE:

Rolipram, a selective inhibitor of cyclic AMP-specific phosphodiesterase (PDE4), has been shown to enhance scopolamine-induced impairment of working memory. However, its effect on reference 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 memory remains to be elucidated.

OBJECTIVES:

To investigate the effects of rolipram on working and reference memories impaired by scopolamine and the involvement of cAMP.

METHODS:

By administration (IP) of rolipram and forskolin, an activator of adenylyl cyclase (AC), the effects of both drugs on the number of correct choices and errors in experiment 1 and, the frequency of both working 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 effective 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 reversing both working and reference memory impairments via increased cyclic AMP concentrations in certain signal transduction pathways, rather than by a generalized increase in cAMP.

PMID:
10923759
[Indexed for MEDLINE]

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