The effect of aniracetam (10, 50, 100 mg/kg i.p. daily for 15 days) on
both behavioural and biochemical parameters was investigated in the a
dult rat. Animals given aniracetam (50 mg/kg 1 h before the trial) sho
wed a significant increase in the percentage of conditioned active avo
idance responses and a reduction of latency times. Aniracetam signific
antly counteracted the scopolamine-induced memory failure at the passi
ve avoidance (step down) test, while it did not modify the locomotion
of the animals. In purified frontocortical and hippocampal synaptic me
mbranes of rats treated with aniracetam (50 mg/kg i.p. daily for 15 da
ys) a potentiation of basal, carbamylcholine-, dopamine- and norepinep
hrine-stimulated adenylyl cyclase activity was observed, while forskol
in-stimulated enzyme activity was not modified. With regard to inosito
l phosphate production measured in fronto-cortical synaptoneurosomes,
aniracetam potentiated the stimulation by angiotensin II, while the st
imulation by carbamylcholine, not affected by 10 and 50 mg/kg aniracet
am, was notably, although not significantly, decreased by 100 mg/kg an
iracetam. Furthermore, in synaptosomes derived from hippocampus, anira
cetam (50 mg/kg i.p. daily for 15 days) caused an increase of both bas
al and K+-stimulated intrasynaptosomal. Ca2+ concentration. In conclus
ion, a correlation between the improvement of behavioural performance
and the modulation of transducing systems by aniracetam seems to take
place in brain areas, such as frontal cortex and hippocampus, known to
play a major role in the control of cognitive functions.