Neurochemical Journal | 2019
The Involvement of the Serotonin, Glutamate, and GABA Receptors in the Manifestation of the Antidepressant-Like Effect of Cycloprolylglycine
Abstract
Abstract—We studied the effect of a 2-week administration of cycloprolylglycine peptide (CPG) (1 and 2 mg/kg/day, i.p.) on the binding characteristics of serotonin 5-HT2A-, NMDA-, metabotropic glutamate mGluII-, GABAA- and GABAB-receptors in the brain of inbred BALB/c mice in vitro and ex vivo. It was found that CPG at doses of 1 and 2 mg/kg/day reduces the density of 5-HT2A receptors in the striatum of mice by 24 and 28%, respectively. A decrease in the density of NMDA receptors in the hippocampus was observed only at a dose of 2 mg/kg/day; it was 22%. At the same time, there was an increase in the density of GABAA receptors in the frontal cortex at a dose of 1 mg/kg/day by 36% compared with the control. The 2-week administration of CPG at both doses did not affect Bmax of mGluII- and GABAB receptors, as well as Kd in all groups. In the in vitro radioligand assay, the CPG did not affect the specific binding of the labeled ligands of the studied receptors. These data indicate the functional involvement of 5-HT2A, NMDA, and GABAA receptors in the formation of the antidepressant-like effect of cycloprolylglycine in BALB/c mice for the first time.