NEUROPSYCHOPHARMACOLOGICAL STUDIES OF A CA2+ CHANNEL BLOCKER ON THE MODULATION OF BRAIN CA2+ MOBILIZATION OF SPONTANEOUSLY HYPERTENSIVE RATS UNDER MILD STRESS

The psychotropic effects of a calcium channel blocker (Ca antagonist) were examined in behavioral studies following changes in Ca-45(2+) influx in synaptosomal fractions of brain tissues using spontaneously hypertensive rats (SHR). Under a novel circumstance utilizing 85-dB noise, SHR demonstrated hyperactivity and a significant increase in Ca-45(2+) uptake into synaptosomal fractions of frontal cortex (FC) and hippocampus. Such hyperactivity may be caused not only be seeking behavior but also by stress-induced anxiety 22. Such hyperactivity was significantly blocked after 10 days of repeated administration of diazepam (DZP), tandospirone (SM-3997; SM), a 5-HT1A anxiolytic, and nitrendipene (Nit), a Ca antagonist. Moreover, repeated administration of DZP, SM and Nit reduced the maximum binding density of H-3-PN200-110 and reduced the Ca-45(2+) uptake in FC of SHR. In hippocampus, midbrain, hypothalamus and striatum, the increased ratio of Ca-45(2+) uptake was reduced after repeated administration of Nit or SM. These results suggest that the hyperactivity induced by this novel circumstance was reduced by DZP, SM and Nit and may be attributed to inhibition of voltage-dependent Ca channel activities in FC. In addition, Nit may induce anti-anxiety through the modulation of Ca2+ mobilization in the central nervous system.