Enhancement of in vivo binding of [123I]beta-CIT by MK-801 in rat brain.
The effects of MK-801, a noncompetitive NMDA receptor antagonist, on in vivo and in vitro binding of radioactive iodine ([123I] or [125I]) labeled beta-CIT [RTI-55, 3beta-(4-iodophenyl)tropane-2beta-carboxylic acid methyl ester] were investigated in rat brain. In the in vitro binding study, 10 pM of [125I]beta-CIT was incubated with either 0.03 microM or 3 microM of MK-801 at 24 degrees C for 60 min. In vitro, no alterations in [125I]beta-CIT binding in any region of rat brain slices were detected after addition of MK-801. In the in vivo binding study, [123I]beta-CIT was intravenously injected into rats 30 min after intraperitoneal injection of 0.03-1 mg/kg of MK-801. The in vivo [123I]beta-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 [123I]beta-CIT binding induced by MK-801 were mainly due to increases in both input rate constant k3 and output rate constant k4. 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.
Nakano
T
T
Division of Tracer Kinetics, Biomedical Research Center, Osaka University Medical School, Suita, Japan.
Takatoku
K
K
Matoba
Y
Y
Iwamoto
B
B
Nishiura
M
M
Inoue
O
O
Nishimura
T
T
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D003042:Cocaine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D018691:Excitatory Amino Acid Antagonists; D007457:Iodine Radioisotopes; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D016291:Dizocilpine Maleate; D003042:Cocaine