Enhancement of in vivo binding of [123I]β-CIT by MK-801 in rat brain

✍ Scribed by Takayuki Nakano; Keizo Takatoku; Yoshinori Matoba; Bunichi Iwamoto; Masaru Nishiura; Osamu Inoue; Tsunehiko Nishimura

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 139 KB
• Volume: 30
• Category: Article
• ISSN: 0887-4476
• DOI: 10.1002/(sici)1098-2396(199812)30:4<402::aid-syn7>3.0.co;2-n

✦ Synopsis

The effects of MK-801, a noncompetitive NMDA receptor antagonist, on in vivo and in vitro binding of radioactive iodine ([ 123 I] or [ 125 I]) labeled ␤-CIT [RTI-55, 3␤-(4-iodophenyl)tropane-2␤-carboxylic acid methyl ester] were investigated in rat brain. In the in vitro binding study, 10 pM of [ 125 I]␤-CIT was incubated with either 0.03 µM or 3 µM of MK-801 at 24°C for 60 min. In vitro, no alterations in [ 125 I]␤-CIT binding in any region of rat brain slices were detected after addition of MK-801. In the in vivo binding study, [ 123 I]␤-CIT was intravenously injected into rats 30 min after intraperitoneal injection of 0.03-1 mg/kg of MK-801. The in vivo [ 123 I]␤-CIT binding in the striatum, frontal cortex, occipital cortex, hypothalamus, and thalamus was significantly increased by pretreatment with 1 mg/kg of MK-801. Kinetic analysis using the cerebellum as a reference region revealed that the increases in in vivo [ 123 I]␤-CIT binding induced by MK-801 were mainly due to increases in both input rate constant k 3 and output rate constant k 4 . The results of this study indicate that the glutamatergic system, including NMDA receptor, plays an important role in regulating neurotransmission in the dopaminergic or serotonergic systems in intact brain.