Psychotropic and Neuroreceptor Effects of Cyclopropylglycine Upon Intranasal Administration

The effects of chronic intranasal administration of cycloprolylglycine (CPG, 1 and 2 mg/kg) on the behavior of BALB/c and C57BL/6 mice and the brain neuroreceptor characteristics in BALB/c mice were studied. Intranasal administration of CPG (1 and 2 mg/kg, 2 weeks) to BALB/c mice in the Porsolt test resulted in a significant antidepressant-like effect more potent than that from intraperitoneal administration of CPG. At the same time, intranasal administration of CPG to C57BL/6 mice in the tail-suspension test was the same as that upon intraperitoneal administration and led to a moderate antidepressant-like effect (1 mg/kg, 4 weeks). Intranasal CPG did not produce any effect on anxiety or exploratory activity in the closed cross-maze test. Radioligand analyses showed an increased density of GABAA receptors in the PFC (1 mg/kg) and reduced density of NMDAand 5HT2A receptors in the hippocampus and striatum, respectively, after intranasal administration of CPG (1 and 2 mg/kg) for two weeks while not affecting mGluII receptor binding in the hippocampus. The significant difference in hippocampal NMDA binding between the two routes may indicate that this receptor is involved in the mechanism of the antidepressant-like effect of CPG.