Is synaptic dopamine concentration the exclusive factor which alters the in vivo binding of [11C]raclopride?: PET studies combined with microdialysis in conscious monkeys.
The effects of dopamine release manipulated by drugs on the in vivo binding of [11C]raclopride in the striatum were evaluated in conscious monkeys combined with microdialysis. The in vivo binding of [11C]raclopride was evaluated by high resolution positron emission tomography (PET), and the dopamine concentrations in the striatal extracellular fluid (ECF) were measured by microdialysis in the same animals. The systemic administration of the direct dopamine enhancers, GBR12909 (a dopamine transporter (DAT) blocker, at 0.5, 2 and 5 mg/kg) or methamphetamine (a dopamine releaser, at 0.1, 0.3 and 1 mg/kg) dose-dependently increased the dopamine concentration in the striatal ECF, and decreased in vivo [11C]raclopride binding in the striatum. The administration of the indirect dopamine modulators benztropine (a muscarinic cholinergic antagonist, at 0.1, 0.3 and 1 mg/kg) or ketanserine (a 5-HT2 antagonist, at 0.3, 1 and 3 mg/kg) also increased dopamine level in the striatal ECF, and decreased [11C]raclopride binding in a dose-dependent manner. However, the plots of percentage change in dopamine concentration in striatal EFC against that in [11C] raclopride binding indicated different relationships between the effects of direct dopamine enhancers (GBR12909 and methamphetamine) and indirect dopamine modulators (benztropine and ketanserine). These results suggested that the alternation of [11C]raclopride binding in vivo as measured by PET was differently affected by different neuronal manipulations, and not simply by the synaptic concentration of dopamine.
Tsukada
H
H
Central Research Laboratory, Hamamatsu Photonics, Hamakita, Shizuoka, Japan. tsukada@crl.hpk.co.jp
Nishiyama
S
S
Kakiuchi
T
T
Ohba
H
H
Sato
K
K
Harada
N
N
D000818:Animals; D002250:Carbon Radioisotopes / Q000097:blood / Q000493:pharmacokinetics*; D002531:Cerebellum / Q000000981:diagnostic imaging* / Q000378:metabolism*; D003243:Consciousness; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000378:metabolism*; D004298:Dopamine / Q000502:physiology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D007700:Kinetics; D008253:Macaca mulatta; D008297:Male; D017551:Microdialysis; D010879:Piperazines / Q000494:pharmacology; D020891:Raclopride / Q000097:blood / Q000493:pharmacokinetics*; D014055:Tomography, Emission-Computed / Q000379:methods
D002250:Carbon Radioisotopes; D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; D020891:Raclopride; C043425:vanoxerine; D004298:Dopamine