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 45Ca2+ 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 45Ca2+ 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. 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 3H-PN200-110 and reduced the 45Ca2+ uptake in FC of SHR. In hippocampus, midbrain, hypothalamus and striatum, the increased ratio of 45Ca2+ uptake was reduced after repeated administration of Nit or SM. These results suggest that the hyperactivity induced by this novel circumstances 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.
Chou
M Y
MY
Department of Pharmacology, Tokyo Medical College, Japan.
Watanabe
Y
Y
Shibuya
T
T
D000161:Acoustic Stimulation; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D004095:Dihydropyridines / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D054833:Isoindoles; D017275:Isradipine; D007700:Kinetics; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009568:Nitrendipine / Q000494:pharmacology*; D009928:Organ Specificity; D010879:Piperazines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D012016:Reference Values; D013315:Stress, Psychological / Q000378:metabolism*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004095:Dihydropyridines; D054833:Isoindoles; D010879:Piperazines; D011743:Pyrimidines; C055267:tandospirone; D009568:Nitrendipine; D003975:Diazepam; D002118:Calcium; D017275:Isradipine