Effects of an apovincaminic acid derivative VA-045 on neuronal activity in rat brain stem reticular formation.
Extracellular single unit and spontaneous cortical electroencephalographic (ECoG) recordings were made in the brain stem reticular formation (RF) and the frontal cortex, respectively, of urethane-anesthetized rats. VA-045, an apovincaminic acid derivative had no significant effects on the spontaneous firing rate of the RF neurons and ECoG. Closed head injury (CHI) was induced by dropping a 400 g weight through a tube from 70 cm on a steel helmet placed on the vertex. CHI led to a reduction in the firing rate of RF neurons and ECoG synchronization. VA-045 dose-dependently reversed the CHI-induced decrease in the firing rate of RF and led to ECoG desyncronization. Clonidine, an alpha 2 adrenoceptor agonist, and scopolamine, a muscarinic receptor antagonist, also reduced the firing rate of RF neurons and led to ECoG synchronization. VA-045 dose-dependently antagonized the effects of clonidine, but not the effects of scopolamine on RF neuronal activity and ECoG. Thus, VA-045 has an ameliorating effect on the CHI-induced depression of neuronal activity in the RF. A central alpha 2 adrenoceptor antagonistic action may be involved.
Okuyama
S
S
Department of Pharmacology, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Kawashima
N
N
Araki
H
H
Otomo
S
S
Shima
K
K
D000818:Animals; D001933:Brain Stem / Q000187:drug effects* / Q000502:physiology; D003000:Clonidine / Q000494:pharmacology; D004569:Electroencephalography / Q000187:drug effects; D016489:Head Injuries, Closed / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; 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; D003000:Clonidine