Endogenous dopamine release induced by repetitive transcranial magnetic stimulation over the primary motor cortex: an [11C]raclopride positron emission tomography study in anesthetized macaque monkeys.
BACKGROUND
Repetitive transcranial magnetic stimulation (rTMS) has been used as a treatment for neuropsychiatric disorders such as depression and Parkinson's disease (PD). Despite the growing interest in therapeutic application of rTMS, precise mechanisms of its action remain unknown. With respect to PD, activation of the mesostriatal dopaminergic pathway is likely to be a candidate mechanism underlying the therapeutic effects; however, modulating effects of rTMS over the primary motor cortex (M1) on the dopaminergic system have not been studied.


METHODS
We used [11C]raclopride positron emission tomography to measure changes of extracellular dopamine concentration after 5Hz rTMS over the M1 in eight anesthetized monkeys.


RESULTS
rTMS over the right M1 induced a reduction of [11C]raclopride binding potential (BP) in the bilateral ventral striatum, including the nucleus accumbens, and a significant increase of BP in the right putamen; no significant BP reduction was found in the dorsal striatum. These data indicate that rTMS over the motor cortex induces a release of endogenous dopamine in the ventral striatum.


CONCLUSIONS
Our results suggest that therapeutic mechanisms of rTMS may be explained in part by an activation of the mesolimbic dopaminergic pathway, which plays critical roles in rewards, reinforcement, and incentive motivation.
Ohnishi
Takashi
T
Department of Investigative Radiology, National Cardio-Vascular Center Research Institute, Osaka, Japan.
Hayashi
Takuya
T
Okabe
Shingo
S
Nonaka
Ikuo
I
Matsuda
Hiroshi
H
Iida
Hidehiro
H
Imabayashi
Etsuko
E
Watabe
Hiroshi
H
Miyake
Yoshihiro
Y
Ogawa
Mikako
M
Teramoto
Noboru
N
Ohta
Yoichirou
Y
Ejima
Norimasa
N
Sawada
Tohru
T
Ugawa
Yoshikazu
Y
D000818:Animals; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000378:metabolism / Q000528:radiation effects; D004298:Dopamine / Q000378:metabolism* / Q000528:radiation effects; D018492:Dopamine Antagonists / Q000493:pharmacokinetics; D004565:Electroconvulsive Therapy / Q000295:instrumentation / Q000379:methods; D004574:Electromagnetic Fields; D008252:Macaca fascicularis; D008297:Male; D009044:Motor Cortex / Q000528:radiation effects*; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000378:metabolism / Q000528:radiation effects; D009714:Nucleus Accumbens / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000528:radiation effects; D011699:Putamen / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000528:radiation effects; D020891:Raclopride / Q000493:pharmacokinetics; D014055:Tomography, Emission-Computed; D050781:Transcranial Magnetic Stimulation / Q000627:therapeutic use
D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D020891:Raclopride; D004298:Dopamine