The Effects of Piracetam and Noopept on NMDA- and 5-HT_2A-Receptors in the Brains of Mice with Congenital -Arrestin Deficiency

Based on the special role of the beta-arrestin signal protein 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, IP), and Noopept (ethyl ether N-phenyl-acetyl-L-prolyl-glycine, GVS-111, 0.5 mg/kg, IP) were studied in mice with congenital deficiency of beta-arrestin-2 (BARR2-KO mice) and in C57Bl/6 mice (wild type for the BARR2-KO, WT strain). Serotonin (5-HT)(2A)) and NMDA-receptors of the brain, which play an important role in cognitive processes but differ in structure and activation mechanism, were chosen as the objects of the study. Using radioligand analysis, it was found that the BARR2-KO mice differ from the C57Bl/6 in significantly higher density (B-max) 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 in both BARR2-KO (Piracetam by 76% and Noopept by 78%) and C57Bl/6 strains (Piracetam by 112% and Noopept by 49%). At the same time, the effects of both drugs on the density of serotonin 5-HT2A-receptors in BARR2-KO and C57Bl/6 mice were 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, in the C57Bl/6, neither Piracetam nor Noopept had any effect. Thus, the absence of the beta-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 mice with congenital beta-arrestin deficiency and in the strain with normal expression may indicate that this type of receptors is a common primary target for the action of nootropics of various structures.