2012 Fiscal Year Final Research Report
The mechanism of general anesthesia investigated in the area of non-synaptic neural transmitting at the extracellular space in the brain: focusing on nitric oxide and dopaminergic system
| Project/Area Number |
22591706
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Anesthesiology/Resuscitation studies
|
|---|
| Research Institution | Nagoya University (2011-2012)
Hamamatsu University School of Medicine (2010) |
|---|
Principal Investigator |
ADACHI Yushi 名古屋大学, 医学部附属病院, 病院講師 (80420355)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SATO Shigehito 浜松医科大学, 医学部, 教授 (30143176)
|
|---|
| Project Period (FY) |
2010 – 2012
|
| Keywords | 非シナプス型細胞伝達 / 細胞外腔 / 一酸化窒素 / ドパミン / 麻酔作用 / ラット / 線条体 / マイクロダイアリシス |
|---|
| Research Abstract |
Pentobarbital (PB) and ketamine (Ket) influence the concentration of neurotransmitters in the brain. PB has been reported to decrease the extracellular nitric oxide (NO) concentration through a decrease in acetylcholine (ACh) release, while Ket has been shown to increase the NO concentration via an increase in ACh release. Here, we investigated effects of PB and Ket on NO release and the relationship between NO and ACh in the rat striatum by in vivo microdialysis experiments. Male Sprague-Dawley rats were used. A microdialysis probe was inserted into the right striatum and perfused with modified Ringer’s solution. Samples were collected every 15 min and injected into an HPLC system. The rats were freely moving, and PB and Ket were administered intraperitoneally. Neostigmine (1 and 10 μM) and mecamylamine (100 μM) were added to the perfusate. Calcium and magnesium concentrations were modified for each anesthetic to influence Ach release. PB decreased NO products (NOx) while Ket increase
… More
d them. While perfusion with neostigmine showed no effect on baseline Nox concentrations, it diminished the PB-inducedNOx reduction at low concentrations and abolished it at high concentrations. Magnesium-free perfusion had no effect on baseline Nox concentrations, whereas perfusion at a low magnesium concentration antagonized the PB-induced Nox reduction. Mecamylamine and calcium-free perfusion had no effect on baseline Nox concentrations and Ket-induced Nox increases. PB may decrease NO release through reduction in Ach release, whereas Ket may increase NO release independent of Ach regulation.Moreover, we studied a series of preliminary investigations and the results suggested that general anesthetics could modify many pathways of neural transmitting in extracellular space as a non-synaptic neural transmission. Not only GABA_A, which is one of well-known target receptors of anesthetics, but also GABA_Breceptor would be involved in as a target of general anesthetics with the current results of changing in releases of Nox. Less
|
