Dopamine D2 receptors are unevenly distributed in the rat hippocampus and are modulated differently than in striatum

doi:10.1016/0922-4106(93)90123-Q

European Journal of Pharmacology: Molecular Pharmacology

Volume 245, Issue 2, 15 April 1993, Pages 157-164

https://doi.org/10.1016/0922-4106(93)90123-Q Get rights and content

Abstract

The characteristics of dopamine (DA) D₂ receptors were studied in rat hippocampus and for comparison in striatum using the [³H]spiperone radioreceptor assay in vitro. D₂ receptors exhibit a bimodal distribution along the length of the hippocampus. Heterogeneity also exists in the transverse axis with high densities in themolecular layers of the subiculum and CA1 plus CA2. As in the striatum, D₂ receptors in both dorsal and ventral hippocampus display high and low affinity states for agonists, but all three regions differ with regard to the percentage of receptors in these states. The modulation of these affinity states by GTP, Mg²⁺ and the iron-chelator, 1,1-O-phenanthroline, differs markedly between dorsal and ventral hippocampus, and between these regions and the striatum. A new model for the modulation of the affinity of D₂ receptors for agonists is presented. These data suggest the presence of regional differences in the composition of the D₂ receptor-regulatory protein complex.

References (40)

S. Bischoff et al.
In vivo [³H]spiperone binding to the rat hippocampal formation: involvement of dopamine receptors
Eur. J. Pharmacol.
(1980)
S. Bischoff et al.
Septo-hippocampal system: target for substituted benzamides
Eur. J. Pharmacol.
(1982)
S. Bischoff et al.
Blockade of hippocampal dopamine (DA) receptors: a tool for antipsychotics with low extrapyramidal side effects
Prog. neuro-Psychopharmacol. Biol. Psychiatry
(1988)
M.-L. Bouthenet et al.
A detailed mapping of dopamine D-2 receptors in rat central nervous system by autoradiography with [¹²⁵I]iodosulpride
Neuroscience
(1987)
A. Bruinink et al.
Detection of dopamine receptors in homogenates of rat hippocampus and other brain areas
Brain Res.
(1986)
A. Closse et al.
In vivo labeling of brain dopamine D₂ receptors using the high-affinity specific D₂ agonist [³H]CV 205–502
Brain Res.
(1988)
T.M. Dawson et al.
D-1 dopamine receptors in the rat brain: autoradiographic localization using [³H]SCH23390
Eur. J. Pharmacol.
(1985)
D.J. De Vries et al.
Magnesium ions reveal nanomolar potency of dopamine at [³H]spiperone labelled D-2 receptors in rat corpus striatum
Eur. J. Pharmacol.
(1985)
A. Dumbrille-Ross et al.
Dopamine agonist high-affinity state in solubilized D₂ receptors in striatum but not in anterior pituitary
Biochem. Pharmacol.
(1987)
M.W. Hamblin et al.
Interactions of agonists with D-2 dopamine receptors: evidence for a single receptor population existing in multiple agonist affinity-states in rat striatal membranes
Biochem. Pharmacol.
(1984)

E. Kari et al.

[³H]Imipramine binding in the retinas of chickens and pigs

Exp. Eye Res.

(1988)

C. Köhler et al.

Dopamine D₂ receptors in the rat, monkey and postmortem human hippocampus. An autoradiographic study using the novel D₂-selective ligand ¹²⁵I-NCQ 298

Neurosci. Lett.

(1991)

E.K. Richfield et al.

Properties of D₂ receptor autoradiography: high percentage of high affinity agonist sites and increased nucleotide sensitivity in tissue sections

Brain Res.

(1986)

P. Seeman et al.

Neuroleptic/dopamine receptors: search for new g-linked receptors

Eur. J. Pharmacol.

(1990)

S.H. Simmonds et al.

Guanine nucleotide effects on agonist binding at D₂ receptors in bovine anterior pituitary

Biochem. Pharmacol.

(1986)

J. Van der Weide et al.

Autoradiographic localization of dopamine D-2 receptors in the rat brain using the new antagonist [³H]N-0437

Neurosci. Lett.

(1987)

C. Verney et al.

Morphological evidence for a dopaminergic terminal field in the hippocampal formation of young and adult

Neuroscience

(1985)

L.S. Benardo et al.

Dopamine modulates a Ca²⁺-activated potassium conductance in mammalian hippocampal pyramidal cells

Nature

(1982)

D. Ben-Shachar et al.

Effect of iron chelators on dopamine D₂ receptors

J. Neurochem.

(1985)

S. Bischoff

Mesohippocampal dopamine system. Characterization, functional and clinical implications

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^☆: Part of this work has been presented at the 9th Congress of the European Neuroscience Association, 8–12 September 1985, Oxford, UK.

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Regular paperDopamine D2 receptors are unevenly distributed in the rat hippocampus and are modulated differently than in striatum☆

Abstract

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Prog. neuro-Psychopharmacol. Biol. Psychiatry

Neuroscience

Brain Res.

Brain Res.

Eur. J. Pharmacol.

Eur. J. Pharmacol.

Biochem. Pharmacol.

Biochem. Pharmacol.

Exp. Eye Res.

Neurosci. Lett.

Brain Res.

Eur. J. Pharmacol.

Biochem. Pharmacol.

Neurosci. Lett.

Neuroscience

Dopamine modulates a Ca2+-activated potassium conductance in mammalian hippocampal pyramidal cells

Nature

Effect of iron chelators on dopamine D2 receptors

J. Neurochem.

Mesohippocampal dopamine system. Characterization, functional and clinical implications

Regular paper
Dopamine D₂ receptors are unevenly distributed in the rat hippocampus and are modulated differently than in striatum☆

Dopamine modulates a Ca²⁺-activated potassium conductance in mammalian hippocampal pyramidal cells

Effect of iron chelators on dopamine D₂ receptors