The Influence of Pantogam and Atomoxetine on Attention Stability and Distribution of Dopamine D2 and GABAB Receptors in the Attention Deficit Mouse Model

Abstract—

The closed enriched cross maze test was employed as a novel experimental model of the attention deficit disorder (ADD) for evaluation of the behavioral and neurochemical effects of the nootropic drug pantogam (100 mg/kg, intraperitoneally) and atomoxetine hydrochloride (3 mg/kg, intraperitoneally) administered subchronically to CD-1 outbred mice. Two subpopulations of rodents spontaneously diverging in attention to enriched compartments (ED-Low and ED-High), were estimated on the basis of time spent by the mice in the empty or enriched compartments. The ED-Low and ED-High mice did not differ in parameters associated with anxiety, exploratory efficacy, and locomotor activity. Subchronic administration of both drugs in selected doses produced a corrective effect on animal behavior manifested as selective increase in the ED-ratio values in the ED-Low subpopulation (p < 0.05). The radioligand binding assays revealed differences in the distribution of dopamine D₂ and GABA_B receptors (B_max) in prefrontal cortex of control ED-Low and ED-High mice. In prefrontal cortex of ED-Low mice treatment with atomoxetine produced a decrease in the B_max values of D₂ receptors by 14%, while pantogam decreased the B_max values of D₂ receptors by 22% (p < 0.05) and increased the B_max values for GABA_B receptor binding by 44%. Thus, subchronic administration of pantogam had a selective corrective effect on the behavior parameters and the density of the studied receptor subtypes in animals having had severe attention deficit in the test.