| Project/Area Number |
10670149
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Pathological medical chemistry
|
|---|
| Research Institution | TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH (1999)
Tokyo Metropolitan Institute for Neuroscience (1998) |
|---|
Principal Investigator |
ONOE Hirotaka Tokyo Metropolitan Institute for Neuroscience, Dept. Psychology, 東京都神経科学総合研究所, 主任研究員 (80214196)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
WATANABE Yashuyoshi Osaka Bioscience Institute, Dept. Neuroscience, 第3部門, 研究部長 (40144399)
|
|---|
| Project Period (FY) |
1998 – 1999
|
| Project Status |
Completed (Fiscal Year 1999)
|
| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥2,400,000 (Direct Cost: ¥2,400,000)
|
|---|
| Keywords | positron emission tomography / GABAィイD2AィエD2 receptor / Benzodiazepine / monkey / Ro15-4513 / limbic system / anterior cingulate / ポジトロンエミッショントモグラフィー |
|---|
| Research Abstract |
Previously, we revealed the presence of very high- and high-affinity binding sites (ex. Kd values in the amygdala are ca. 0.4 and 18.7 nM, respectively) in the γ-aminobutyric acid/benzodiazepine (GABAィイD2AィエD2/BZ) receptor in the living monkey brain by an in vivo saturation study using ィイD111ィエD1C-labeled Ro15-4513 with high specific radioactivity (>70 GBq/μmol). To assess the physiological function of the very high-affinity binding sites of GABAィイD2AィエD2/Benzodiazepine (BZ) receptor in the intact living brain, the binding of a ィイD111ィエD1C-labeled BZ partial inverse agonist ([ィイD111ィエD1C]Ro15-4513) of the GABAィイD2AィエD2/BZ receptor was investigated by the positron emission tomography (PET) with conscious and anesthetized monkeys. In the conscious monkey, sleep deprivation or ketamine, a NMDA receptor blocker, treatment increased the binding of [ィイD111ィエD1C]Ro15-4513, but not did that of [ィイD111ィエD1C]Ro15-1788. Furthermore, propofol, a positive allosteric modulator of the GABAィイD2AィエD2/BZ receptors, anesthesia induced decreases in the binding of [ィイD111ィエD1C]Ro15-4513 but not did that of [ィイD111ィエD1C]Ro15-1788. The very high affinity binding sites of [ィイD111ィエD1C]Ro15-4513 were invisible in the most of limbic regions under the propofol anesthesia. These results strongly indicate that the binding characteristics of the [ィイD111ィエD1C]Ro15-4513 in vivo may be related to both the heterogeneity of GABAィイD2AィエD2/BZ receptor and its efficacy modulated by allosteric agents in the living brain.
|
