Localization of dopamine receptors in the tree shrew brain using [3H]-SCH23390 and [125I]-epidepride

doi:10.1016/S0006-8993(99)01795-3

Brain Research

Volume 841, Issues 1–2, 11 September 1999, Pages 101-113

https://doi.org/10.1016/S0006-8993(99)01795-3 Get rights and content

Abstract

The tree shrew is a mammalian species, which is phylogenetically related to insectivores and primates. The aim of the present study was to investigate the distribution of dopamine receptor D1- and D2-like binding sites in the brain of this non-rodent, non-primate mammal. Using in vitro autoradiography and employing the radioligands [ $^{3} H$ ]-SCH23390 and [ $^{125} I$ ]-epidepride, dopamine receptors were mapped and quantified. Significant findings with regard to the D1-like binding pattern include the presence of a “patchy” binding in the striatum. In the cortex, D1-like binding sites were observed in both the superficial and the deep layers. In the hippocampal formation, D1-like binding sites were seen primarily in the CA1 region and not in the dentate gyrus. These characteristics of the D1 pattern in the tree shrew brain are shared by cat and monkey and human brain, but not by rodent brain. Significant findings with regard to the D2-like binding pattern include the presence of D2-like binding in the claustrum. In addition, the striatum demonstrated “patchy” D2-like binding. These characteristics of the D2 pattern in the tree shrew brain are shared by cat and monkey and human brain, but not by rodent brain. On the other hand, the significant densities of D2-like binding sites in the glomerular layer of the tree shrew olfactory bulb is a finding that discriminates tree shrews from higher evolutionary species who lack such binding. Overall, the evidence coincides with the view that tree shrews are phylogenetically related to primates.

Introduction

The dopamine system is a phylogenetically old system and the neurotransmitter dopamine is present in the CNS of all vertebrate species investigated so far [see Ref. [38]]. The central actions of dopamine may be mediated by multiple dopamine receptor subtypes, which are currently classified as D1-like or D2-like receptors based on pharmacological and functional criteria [21]. Receptors belonging to the D1-like subfamily (D1 and D5) are positively linked to adenylate cyclase [35], whereas D2-like receptors (D2, D3, D4) appear negatively linked to adenylate cyclase or coupled to other transduction pathways [34].

In all species investigated so far, the highest densities of D1- and D2-like receptors are found in the basal ganglia [see for example Refs. 3, 4, 9, 41, 47]. In these regions of the brain, the distribution of both receptor types appears to be conserved throughout species 4, 39. Outside the basal ganglia, however, considerable species differences may exist, such as in the superior colliculus, the olfactory bulb, the ventral tegmental area, the septum and the cerebellum [4]. The latter brain regions were shown to contain significant levels of dopamine receptors in lower vertebrate species, such as rats and mice, but low or undetectable levels in higher vertebrate species, such as cats, monkeys and humans [4]. Furthermore, species-specific distribution patterns were observed in the hippocampus and in cortical regions [4]. The tree shrew is a non-rodent mammalian species, which is phylogenetically located between insectivores and primates [31]. Nowadays, tree shrews are accorded to their own order Scandentia [31]. In view of the proposed species differences in dopamine receptor localization, the aim of the present study was to investigate the distribution of dopamine D1- and D2-like receptors in this non-rodent, non-primate mammal. We used the radioligand [ $^{125} I$ ]-epidepride, a compound which combines a very high affinity for D2-like receptors with a very low non-specific binding. In the past, this ligand has proven particularly suitable for visualization of brain areas with low numbers of D2-like receptors 18, 22.

Section snippets

Materials and methods

Four adult female tree shrews (Tupaia belangeri) from the breeding colony at the German Primate Center were used for this study. All animals were housed singly on a regular day/night cycle (lights on from 0800 to 2000 h) and were used to handling. Tree shrews were decapitated between 0800 and 0900 h, their brains were quickly removed and frozen over liquid nitrogen. With a cryostate, adjacent 10 μm sections were cut for D1-binding, D2-binding and Nissl staining. Sections were cut throughout the

Results

For descriptional purposes, binding densities referred to below as `very high' correspond to densities higher than 66% of the rostral caudate nucleus (rCaudate), densities designated as `high' range between 33% and 66% of rCaudate, `moderate' densities range between 10% and 33% of rCaudate and `low' densities correspond to densities below 10% of rCaudate.

Discussion

In the present study, dopamine receptors were observed in the basal ganglia nuclei, the amygdaloid complex, cortical areas, the hippocampal formation, the thalamus, the hypothalamus, the midbrain and the brainstem of the tree shrew brain. The demonstration of dopamine receptors in these areas of the brain is in line with numerous earlier reports on dopamine receptor mapping in other mammalian species 1, 4, 6, 7, 8, 20, 24, 25, 28, 30, 39, 40, 41, however, a few differences were noted and will

Abbreviations

ABmc	Accessory basal amygdaloid nucleus, magnocellular part
ABpc	Accessory basal amygdaloid nucleus, parvocellular part
ABs	Accessory basal amygdaloid nucleus, superficial part
Acb	Nucleus accumbens
AqS	Aquaductus Sylvii
Bmc	Basal amygdaloid nucleus, magnocellular part
Bpc	Basal amygdaloid nucleus, parvocellular part
C	Caudate nucleus
ca	Anterior commissure
CA1,pyr	CA1 stratum pyramidale
CA1,so	CA1 stratum oriens
CA1,sr	CA1 stratum radiatum
CA3,pyr	CA3 stratum pyramidale
CA3,so	CA3 stratum oriens
CA3,sr/l	CA3 stratum

Acknowledgements

This study was supported by an EC-TMR (ERB4001GT962992) to M.J.M. and DAAD (A/95/01431) to E.I.

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Research reportLocalization of dopamine receptors in the tree shrew brain using [3H]-SCH23390 and [125I]-epidepride

Abstract

Introduction

Section snippets

Materials and methods

Results

Discussion

Abbreviations

Acknowledgements

Neuroscience

Brain Res.

Neuroscience

Neuroscience

Neuroscience

Neuroscience

Pharmacol. Biochem. Behav.

Brain Res.

Life Sci.

Neurosci. Lett.

Neurosci. Lett.

Neuroscience

Eur. J. Pharmacol.

Brain Res.

Brain Res.

Quantitative autoradiographic localization of the D1 and D2 subtypes of dopamine receptors in rat brain

J. Neurosci.

Autoradiographic localization of dopamine D 1 and D 2 receptors in the brain of several mammalian species

J. Neural. Transm.: Gen. Sect.

Dopamine D2 receptors in the rat brain: autoradiographic visualization using a high-affinity selective agonist ligand

J. Neurosci.

D-1 dopamine receptors in the rat brain: a quantitative autoradiographic analysis

J. Neurosci.

Quantitative autoradiographic localization of central dopamine D-1 and D-2 receptors

Adv. Exp. Med. Biol.

Dynamics of central nervous 5-HT1A-receptors under psychosocial stress

J. Neurosci.

Monoamine receptors in the amygdaloid complex of the tree shrew (Tupaia belangeri)

J. Comp. Neurol.

Dopamine D2 receptor expression in hippocampus and parahippocampal cortex of rat, cat, and human in relation to tyrosine hydroxylase-immunoreactive fibers

Hippocampus

Research report
Localization of dopamine receptors in the tree shrew brain using [ $^{3} H$ ]-SCH23390 and [ $^{125} I$ ]-epidepride