Effect of sensory stimulus on striatal dopamine release in humans and cats: a [ 11C]raclopride PET study

Abstract

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. Objectives: To visualize in vivo this modification of striatal DA release in healthy human volunteers using Positron Emission Tomography (PET) and [ 11C]raclopride. Experiments in humans were paralled by experiments in anesthetized cats. Changes in endogenous DA release were assessed through its competition with [ 11C]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 [ 11C]raclopride binding remained unchanged by sensory stimuli in both humans and cats. Conclusion: 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 [ 11C]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.