Effects of VA-045, a novel apovincaminic acid derivative, on age-related impairment evidence in electroencephalograph, caudate spindle, a passive avoidance task and cerebral blood flow in rats.
1. The ability of VA-045 to improve aged-related impairment on electroencephalograph (EEG), caudate spindle, performance on a passive avoidance task and cerebral blood flow (CBF) were evaluated in rats. 2. The cortical EEG of the aged rats showed a higher incidence of spontaneous spindle burst (SSB) than seen in young rats. VA-045 decreased the incidence of SSB in aged rats. In contrast, vinpocetine increased the incidence of SSB in aged rats. 3. Electrical stimulation of the striatum in aged rats lead to a higher incidence of neocortical high voltage spindle (CS) than seen in young rats. In young rats, VA-045 had no effect on the CS, whereas an age-related increase in CS was blocked by VA-045, but was enhanced by vinpocetine. 4. There were no differences in the cortical EEG arousal response elicited by stimulation of the reticular formation of the brain stem in rats of all ages. VA-045 and vinpocetine had no effect on the cortical EEG arousal response in both young and aged rats. 5. VA-045, but not vinpocetine, attenuated the age-related decreased step through latency (STL) on a passive avoidance task. VA-045 and vinpocetine did not enhance the acquisition of learning behavior in a passive avoidance task in young rats. 6. VA-045 increased the cerebral blood flow (CBF) in both young and aged rats and the potency in aged rats was greater than that in young rats. Vinpocetine had no effect on CBF in either young or aged rats. 7. The pharmacological effects of VA-045 on age-related neuronal dysfunction are discussed.
Okuyama
S
S
Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Hashimoto-Kitsukawa
S
S
Ogawa
S
S
Imagawa
Y
Y
Kawashima
K
K
Kawashima
Y
Y
Araki
H
H
Otomo
S
S
D000375:Aging / Q000187:drug effects* / Q000502:physiology*; D000818:Animals; D001143:Arousal / Q000187:drug effects; D001362:Avoidance Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D002421:Caudate Nucleus / Q000187:drug effects* / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology*; D003342:Corpus Striatum / Q000502:physiology; D004558:Electric Stimulation; D004569:Electroencephalography / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*; D014748:Vinca Alkaloids / Q000494:pharmacology*
D014665:Vasodilator Agents; D014748:Vinca Alkaloids; C081044:2-(nitrooxy)ethyl apovincaminate; C013983:vinpocetine