Effect of sensory stimulus on striatal dopamine release in humans and cats: a [(11)C]raclopride PET study.
BACKGROUND
Sensory stimulation of the forelimb extremities constitutes a well-established experimental model that has consistently shown to activate dopamine (DA) neurotransmission in the mammals' forebrain.


OBJECTIVE
To visualize in vivo this modification of striatal DA release in healthy human volunteers using Positron Emission Tomography (PET) and [(11)C]raclopride. Experiments in humans were paralleled by experiments in anesthetized cats. Changes in endogenous DA release were assessed through its competition with [(11)C]raclopride binding (BP(raclo)), a radioligand probing DA D2-receptors.


RESULTS
In humans no significant difference of BP(raclo) in caudate (with sensory stimulation: 2.0 +/- 0.3 versus without sensory stimulation: 2.2 +/- 0.3; P = 0.3) or putamen (2.6 +/- 0.3 versus 2.6 +/- 0.2; P = 0.9) ipsilateral to the stimulus was disclosed as a result of sensory stimulation. Similarly, no change of BP(raclo) was observed contralaterally to the stimulation in the caudate nucleus (with sensory stimulation: 2.0 +/- 0.4 versus without sensory stimulation: 2.1 +/- 0.2; P = 0.5) and the putamen (2.5 +/- 0.4 versus 2.6 +/- 0.2; P = 0.4). In cats the same results were obtained in the ipsilateral to stimulation striatum (with sensory stimulation: 2.5 +/- 0.03 versus without sensory stimulation: 2.4 +/- 0.05; P = 0.7). No change was also observed contralaterally to the stimulation (2.4 +/- 0.04 versus 2.5 +/- 0.06; P = 0.6). The [(11)C]raclopride binding remained unchanged by sensory stimuli in both humans and cats.


CONCLUSIONS
This suggests that the DA release induced by sensory stimulus is mostly extrasynaptic whereas the synaptic DA release is probably small, which fits well with the absence of [(11)C]raclopride displacement. The mechanism of this extrasynaptic DA release could be related to a local action of glutamate on dopaminergic terminals via a thalamo-cortico-striatal loop. Present results also underline homology between cat and human responses to sensory stimuli and validate the use of cat brain to find physiological concepts in humans.
Thobois
Stephane
S
Service de Neurologie D and INSERM U 534, Hopital Neurologique et Neurochirurgical Pierre Wertheimer, Lyon, France. s.thobois@ion.ucl.ac.uk
Hassoun
Waddad
W
Ginovart
Nathalie
N
Garcia-Larrea
Luis
L
Le Cavorsin
Marion
M
Guillouet
Stephane
S
Bonnefoi
Frederic
F
Costes
Nicolas
N
Lavenne
Franck
F
Broussolle
Emmanuel
E
Leviel
Vincent
V
D000328:Adult; D000368:Aged; D000818:Animals; D002415:Cats; D002421:Caudate Nucleus / Q000000981:diagnostic imaging / Q000378:metabolism; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D008297:Male; D008475:Median Nerve / Q000502:physiology; D017551:Microdialysis; D008875:Middle Aged; D017072:Neostriatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011699:Putamen / Q000000981:diagnostic imaging / Q000378:metabolism; D020891:Raclopride; D019275:Radiopharmaceuticals; D013045:Species Specificity
D018492:Dopamine Antagonists; D019275:Radiopharmaceuticals; D020891:Raclopride; D004298:Dopamine