Subchronic Administration of Noopept and Semax Peptides Increases the Density of Cortical GABAA-Receptors in the Brain of BALB/c Mice

—The effects of noopept (1 mg/kg/day) and semax (0.6 mg/kg/day) on ex vivo [ 3 H]-muscimol binding to GABA A -receptors in the prefrontal cortex of inbred BALB/c and C57BL/6 mice were examined after subchronic intraperitoneal (i.p.) and intranasal (i.n.) administration known to produce nootropic and anxiolytic activity in BALB/c but not in C57BL/6 mice. It was found that the initial specific binding ( B max ) and dissociation constants ( K d ) for GABA A -receptors do not differ significantly between the two strains. However, in BALB/c mice i.p. noopept and semax administration increased GABA A -receptor density by 38 and 68% compared to the control group whereas after i.n. administration the increase was by 18 and 37%, respectively, which is in accord with the data on a more pronounced anxiolytic effect of i.p. peptide administration than i.n. administration. However, none of the drugs exerted a significant effect on the characteristics of GABA A -receptors in C57BL/6 mice, except for noopept, which decreased the B max value by 20% after i.p. administration. The similarity of noopept and semax effects on the GABA A -receptor density for both administration routes as well as the correlation of these changes with the intensity of anxiolytic effects depending on the administration route may indicate the involvement of GABA A -receptors in the mechanisms underlying the anxiolytic effects of these peptides.