Endogenous dopamine limits the binding of antipsychotic drugs to D3 receptors in the rat brain: a quantitative autoradiographic study
Abstract
[3H]7-hydroxy-N,N-di-n-propyl-2-aminotetralin was used as a radioligand for the autoradiographic measurements of dopamine D3 receptors in rat and human brain. Preincubation of the brain sections was necessary to obtain binding of the radioligand in the islands of Calleja and in the nucleus accumbens, but not in cerebellar lobules 9/10 of the rat. D3 receptors were also totally occluded in unwashed sections of the human striatum. The radioligand binding to D3 receptors was maximal after preincubating the sections for at least 10 min. Pretreatment of the animals with reserpine or tetrabenazine, which results in a severe depletion of endogeneous monoamines, strongly reduces the occlusion of D3 receptors in unwashed brain sections. The occlusion of dopamine D3 receptors in brain sections suggests that the in vivo access to D3 receptors may be locally inhibited by endogenous dopamine. The in vitro binding affinities of 12 antipsychotic drugs for D2 and D3 receptors were evaluated in competition binding experiments, using both rat and cloned human receptors. Most of the compounds showed only a slightly lower affinity for D3 than for D2 receptors in vitro. Affinities of the antipsychotic drugs for cloned human D21 and D3 receptors wer...Continue Reading
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