| Abstract: | S 9977 (1,3,7-trimethyl 8-[3-(4-diethylaminocarbonyl-l-piperazinyl)1-propyl]-3,7-dihydro(1H)2,6-purinedione hydrochloride) is a methylxanthine derivative lacking activity at adenosine receptors and having no phosphodiesterase inhibitory action, but which has been reported to enhance cholinergic function. In mice 0.06 mg/kg ip increased, whereas 0.25 and 1 mg/kg ip decreased, spontaneous alternation in a T-maze. Doses of 0.03 and 0.06 mg/kg ip improved acquisition and retention of a spatial discrimination task when administered on the test days. The dose of 0.06 mg/kg ip was without effect on subsequent retention when given immediately post-acquisition, suggesting it was without effect on storage processes. When it was administered for 14 days prior to testing 0.06 mg/kg ip retained its effects on acquisition and retention of the discrimination task, but no longer had significant effects on spontaneous alternation. In rats, there was no effect on between-day habituation of exploration or on acquisition of a working and reference memory task with a 24 h intertrial interval. However, 0.06 mg/kg ip significantly improved retention of this task and 0.12 mg/kg ip significantly improved acquisition when a 48-h intertrial interval was used, mainly due to a reduction in working memory errors. In a test of reference memory in a helical maze 0.03 mg/kg ip improved acquisition. These results suggest that low, but not high, doses of S 9977 can improve acquisition in tasks relying on both working and reference memory and also can improve performance on retention tasks. The results are discussed with reference to the effects of S 9977 in enhancing cholinergic function. © Wiley-Liss, Inc. |
