Biomedical Engineering Reference
In-Depth Information
20
Dopamine Receptor Binding
and Quantitative Autoradiographic Study
Beth Levant
1. Introduction
The central nervous system (CNS) dopamine system plays an important
role in mediating the reinforcing effects of drugs of abuse
(1)
. In addition,
dopamine receptors have been the principal target of drugs employed in the
treatment of neuropsychiatric disorders such as schizophrenia and Parkinson's
disease. Until 1990, the dopamine receptor population in the brain and periphery
was believed to consist of two subtypes, D
1
and D
2
, which were distinguished by
their pharmacology and coupling to signal transduction systems (for review
see
ref.
2
). D
1
and D
2
receptors exhibit similar distributions in brain with the highest
densities in the striatum (for review
see
ref.
3
). A number of selective radioli-
gands have been synthesized and extensively used to characterize the classical
dopamine receptor subtypes. These radioligands include the D
1
-selective
ligands [
3
H]SCH 23390 and [
125
I]SCH 23982. D
2
receptor-selective ligands
include the antagonists [
3
H]spiperone, [
3
H]YM 09151-2, and [
125
I]iodosulpiride
and the agonists [
3
H]propylnorapomorphine and [
3
H]quinpirole.
Molecular cloning efforts have revealed additional dopamine receptor
subtypes: the D
3
and D
4
subtypes, which have homology with D
2
; and the D
5
which has homology with D
1
(4-6)
. These novel subtypes are expressed in
roughly 10- to 100-fold lower density than the classical dopamine receptor
subtypes. D
3
sites are preferentially localized in limbic brain regions such as the
nucleus accumbens and islands of Calleja. D
4
sites are of greatest abundance in
regions such as the frontal cortex. The distribution of D
5
receptors, as assessed
by D
5
mRNA, appears to be similar to that of the D
1
receptors. Because of the
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