The Effect of Piracetam and Noopept on NMDA and 5-HT_2A Receptors in the Brain of Mice with Congenital β-Arrestin Deficiency

Abstract

Based on the special role of the signal protein β-arrestin in the processes of neuronal plasticity and receptor activation, the effects of the nootropic drugs Piracetam (2-oxo-1-pyrrodinyl-acetamide, UCB 6215, 200 mg/kg, I.P.) and Noopept (ethyl ether N-phenyl-acetyl-L-prolyl-glycine, GVS-111, 0.5 mg/kg, I.P.) in mice with congenital deficiency of β-arrestin-2 (BARR2-KO mice) and in mice of the C57Bl/6 line (wild type for the BARR2-KO, WT line). Serotonin (5-HT2A) and NMDA-receptors of the brain, which play an important role in cognitive processes, but differ in the type of structure and activation mechanism, were chosen as the object of the study. Using radioligand analysis, it was found that the BARR2-KO mouse line differs from the C57Bl/6 mice by a significantly higher density (Bmax) of both NMDA-receptors in the hippocampus (by 85%) and 5-HT2A -receptors in the cerebral cortex (by 54%). Interestingly, both drugs after chronic administration increased the number of NMDA-receptors in the hippocampus both in the BARR2-KO strain (Piracetam – by 76%, Noopept – by 78%) and in the C57Bl/6 strain (Piracetam – by 112%, Noopept – by 49%). At the same time, the effect of both drugs on the density of serotonin 5-HT2A-receptors in BARR2-KO and C57Bl/6 mice was not the same. In particular, Piracetam caused an increase in the density of 5-HT2A-receptors in the cerebral cortex of BARR2-KO mice by 31%, whereas on the comparison line C57Bl/6 neither Piracetam nor Noopept had any effect. Thus, the absence of the β-arrestin signaling protein in BARR2-KO mice is accompanied by an increase in the density of NMDA- and 5-HT2A-receptors in the brain. At the same time, the different effects of Piracetam and Noopept on NMDA receptors both in the line with congenital β‑arrestin deficiency and in the line with normal expression may indicate that this type of receptor is a common primary target for the action of nootropics of various structures.