Ketamine alters the availability of striatal dopamine transporter as measured by [(11)C]beta-CFT and [(11)C]beta-CIT-FE in the monkey brain.
The effects of ketamine anesthesia on the binding of [(11)C]-labeled cocaine analogs, [(11)C]beta-CFT (2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane) and [(11)C]beta-CIT-FE (N-(2-fluoroethyl)-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane), to the striatal dopamine transporter (DAT) were evaluated in the monkey brain using positron emission tomography (PET). We sequentially measured the kinetics of these labeled compounds in the brains of five young-adult male rhesus monkeys (Macaca mulatta) in the conscious state, followed by those under ketamine anesthesia with continuous infusion (3 and 10 mg/kg/h). After intravenous injection, [(11)C]beta-CFT and [(11)C]beta-CIT-FE were predominantly accumulated in the striatum in both conscious and ketamine-anesthetized states. In the conscious state, the striatal uptake of [(11)C]beta-CFT and [(11)C]beta-CIT-FE continuously increased with time up to 91 min after injection. Continuous infusion of ketamine-induced higher levels of uptake of [(11)C]beta-CFT and [(11)C]beta-CIT-FE into the brain in a dose-dependent manner as compared with conscious state, and kinetic analysis with metabolite-corrected arterial input function indicated that the binding potentials (BP = k(3)/k(4)) of both compounds were elevated by ketamine. Not only [(11)C]beta-CIT-FE but also [(11)C]beta-CFT reached the equilibrium state of specific binding in the striatum within 40-50 min after injection. The present results demonstrated that ketamine significantly alters the DAT availability as measured with [(11)C]beta-CFT and [(11)C]beta-CIT-FE in the brain.
Tsukada
H
H
Central Research Laboratory, Hamamatsu Photonics K.K., Shizuoka 434-8601, Japan. tsukada@crl.hpk.co.jp
Nishiyama
S
S
Kakiuchi
T
T
Ohba
H
H
Sato
K
K
Harada
N
N
D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D000818:Animals; D002250:Carbon Radioisotopes; D002560:Cerebrovascular Circulation; D003042:Cocaine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D003287:Contrast Media; D003342:Corpus Striatum / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D007649:Ketamine / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D009662:Nortropanes / Q000493:pharmacokinetics; D013997:Time Factors; D014055:Tomography, Emission-Computed
D000778:Anesthetics, Dissociative; D002250:Carbon Radioisotopes; D003287:Contrast Media; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; C097058:N-(2-fluoroethyl)-2-carbomethoxy-3-(4-iodophenyl)nortropane; D009419:Nerve Tissue Proteins; D009662:Nortropanes; C021279:(1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester; D007649:Ketamine; D003042:Cocaine