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


OBJECTIVE
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.


CONCLUSIONS
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.
Department of Pharmacology and Therapeutics, Louisiana State University Medical Center, Shreveport 71130, USA. hzhang@lsumc.edu
H T
HT
Zhang
J M
JM
O'Donnell
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004347:Drug Interactions; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects*; D008570:Memory, Short-Term / Q000187:drug effects*; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020889:Rolipram / Q000494:pharmacology*; D012601:Scopolamine / Q000494:pharmacology*
D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D018727:Muscarinic Antagonists; D005576:Colforsin; D012601:Scopolamine; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases; D020889:Rolipram