EFFECT OF ALAPTIDE, ITS ANALOGS AND OXIRACETAM ON MEMORY FOR AN ELEVATED PLUS-MAZE IN MICE

In the present study, the elevated plus-maze was used to evaluate memo ry in female mice. In Experiment 1, the mice retested on day 1, 4 or 7 after the initial session escaped from the open arm into the enclosed arm in a significantly shorter time than those retested on day 10 or 14. Thus, a 10-day inter-session interval was chosen for testing drugs which were expected to enhance memory. In Experiment 2, in the retest performed on day 10, both alaptide (cyclo(L-alanyl-1-amino-1-cyclopen tanecarbonyl)) and oxiracetam, given immediately after the Ist session , reduced the transfer latency from the open arm into the enclosed arm as compared with that of the controls. In Experiment 3, a similar eff ect, i.e., the retention of spatial information, was facilitated by po st-session injections of 5 out of 21 alaptide analogues. The new compo unds represent the 2,5-piperazinedione derivatives which contain 1-ami no-1-cyclo-alkanecarboxylic acid (C3 to C7 ring). The cyclopentane- an d cyclohexane-ring was substituted by an alkyl group. In the series wi th the cycloalkane ring, the importance of the structure of alaptide w as confirmed again, which underlines the importance of the cyclopentan e ring; the active structures had L-alanine instead of glycine as the second amino acid. Isomers of the cyclohexane series which contained m ethyl or tert-butyl were most active when the substitution was at posi tion 3. Our results demonstrate that the model of long-term memory can be used to discriminate between closely related chemical structures.