Autoradiographic evidence for the occlusion of rat brain dopamine D 3 receptors in vivo

Abstract

[ 125I]Iodosulpride binding was studied in frontal rat brain sections by quantitative autoradiography. Using preincubated ( = washed) sections, selective labelling and identification of dopamine D 3 receptors was obtained using 0.2 nM [ 125I]iodosulpride in the presence of 100 nM domperidone for the occlusion of the D 2 receptors. A high density of D 3 receptors was noticed in the islands of Calleja. When preincubation of the sections was omitted, no D 3 receptor labelling could be achieved, indicating tight binding to the receptor of an endogenous inhibitor. Such a tight receptor occupancy was not observed for the D 2 receptor and various other neurotransmitter receptors. The occlusion of the D 3 receptor could be prevented by tetrabenazine-induced monoamine depletion of the rats. It can be concluded, therefore, that D 3 receptors are massively occupied by a monoamine, likely to be dopamine. This observation prompts the question to what extent dopamine D 3 receptors can become occupied in vivo by systematically applied exogenous compounds.