ИСТИНА

Prolin-containig dipeptide Noopept (NP) is a structural analog of piracetam, one of the first generation nootropics – racetam group. Like piracetam, NP demonstrates wide spectrum of cognition improvement as well as neuroprotective properties in vivo and in vitro although at much lower doses. Although the effectiveness of NP was shown in a number of studies, the mechanism of its action, cellular targets as well as affected signaling pathways are still poorly understood. Our previous study demonstrated, that NP significantly increased AP frequency in stratum radiatum (SR) interneurons and the frequency of AP dependent IPSC in pyramidal cells. We also showed that NP increase the frequency of spontaneous Ca transients in regional specific manner in cultured hippocampus slices. Taking into account the involvement of cholinergic transmission in the effect of NP (Ostrovskaya et al., 2001; Belnik et al.,2007) we hypothesized that Ca-permeable α7 containing nicotinic AChR (nAChRs) on SR interneurons could be considered as a postsynaptic targets for NP. To test this hypothesis we performed experiments using methillycaconitine (MLA) selective antagonists of alpha7-containing nAChRs. In the set of experiments where NP (5mkM) increased frequency of GABAergic postsynaptic currents (PSCs) recorded fromCA1 pyramidal cells to 203±36% (p<0.05, n=5) subsequent bath application of MLA (100nM) reduced this effect to103±14%.In another set of experiments, where slices were pretreated by MLA ( frequency of PSCs- 89±11%) effect of NP was not manifested. Thus, it is tempting to speculate that NP mediates its effect through the activation of nAChRs in hippocampal interneurons.