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Journal of Neuroscience, Vol 10, 2125-2138, Copyright © 1990 by Society for Neuroscience
Overlap of dopaminergic, adrenergic, and serotoninergic receptors and complementarity of their subtypes in primate prefrontal cortex
PS Goldman-Rakic, MS Lidow and DW Gallager
Section of Neuroanatomy, Yale University School of Medicine, New Haven, Connecticut 06510.
Quantitative in vitro autoradiography was used to determine and compare the
areal and laminar distribution of the major dopaminergic, adrenergic, and
serotonergic neurotransmitter receptors in 4 cytoarchitectonic regions of
the prefrontal cortex (Walker's areas 12, 46, 9, and 25) in adult rhesus
monkeys. The selective ligands, 3H-SCH- 23390, 3H-raclopride, 3H-prazosin,
and 3H-clonidine were used to label the D1 and D2 dopamine receptor
subtypes and the alpha 1- and alpha 2- adrenergic receptors, respectively,
while 125I-iodopindolol was used to detect beta-adrenergic receptors. The
radioligands, 3H-5- hydroxytryptamine and 3H-ketanserin labeled,
respectively, the 5-HT1 and 5-HT2 receptors. Densitometry was performed on
all cortical layers and sublayers for each of the 7 ligands to allow
quantitative as well as qualitative comparison among them in each
cytoarchitectonic area. Although each monoamine receptor was distributed in
a distinctive laminar-specific pattern that was remarkably similar from
area to area, there was considerable overlap among the dopaminergic,
adrenergic, and serotoninergic receptors, while subtypes of the same
receptor class tended to have complementary laminar profiles and different
concentrations. Thus, the D1 dopamine, the alpha 1- and alpha 2-
adrenergic, and the 5-HT1 receptors were present in highest relative
concentration in superficial layers I, II, and IIIa (the "S" group). In
contrast, the beta 1- and beta 2-adrenergic subtypes and the 5-HT2 receptor
had their highest concentrations in the intermediate layers, IIIb and IV
(the "I" group), while the D2 receptor was distinguished by relatively high
concentrations in the deep layer V compared to all other layers (the "D"
class). Consequently, clear laminar differences were observed in the D1 vs
D2 dopaminergic, the alpha- vs beta- adrenergic, and the 5-HT1 vs 5-HT2
serotoninergic receptor subtypes in all 4 areas examined. The anatomical
overlap of different monoaminergic receptors in the same cortical strata
suggests that there may be families of receptors linked by localization on
common targets, while the complementary laminar distribution of the D1 vs
D2, the 5-HT1 vs 5- HT2 and the alpha- vs beta-adrenergic receptors raises
the possibility that different subtypes within a given class may have
distinctive actions in cortex by virtue of their localization on different
cells or possibly different portions of the same cell. Understanding the
anatomical arrangement of receptors within the cortical layers may aid in
the analysis of monoaminergic modulation of higher cortical function.
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