Distribution of the histaminergic neuron system in the central nervous system of rats; a fluorescent immunohistochemical analysis with histidine decar☐ylase as a marker

doi:10.1016/0006-8993(84)90811-4

Brain Research

Volume 295, Issue 1, 12 March 1984, Pages 13-25

https://doi.org/10.1016/0006-8993(84)90811-4 Get rights and content

Abstract

The distribution of histidine decar☐ylase-like immunoreactivity (HDCI) in the rat central nervous system was studied by the indirect immunofluorescence technique. HDCI cell bodies were concentrated in the posterior hypothalamic area, such as in the tuberal magnocellular nucleus, caudal magnocellular nucleus, posterior hypothalamic nucleus and lateral hypothalamus just lateral to the fasciculus mammillothalamicus at the level of the posterior hypothalamic nucleus. Extensive networks of HDCI fibers of various densities were found in many areas of the brain; they were particularly dense in the hypothalamus but were also found in the following areas: rostrally in the cerebral cortex, olfactory nuclei, medial amygdaloid nucleus, n. tractus diagonalis, and bed nucleus of the stria terminals, and caudally in the central gray matter of the midbrain and pons, auditory system, n. vestibularis medialis, n. originis nervi facialis, n. parabrachialis, n. commissuralis, n. tractus solitarii, and n. raphe dorsalis.

Reference (50)

Ben-AriY. et al.
Histamine synthesizing afferents within the amygdaloid complex and bed nucleus of the stria terminalis of the rat
Brain Research
(1977)
EllouzF. et al.
Minimal structural requirements for adjuvant activity of bacterial peptidoglycan derivatives
Biochem. biophys. Res. Commun.
(1974)
FukuiH. et al.
Immunochemical cross reactivity of the antibody elicited againstl-histidine decar☐ylase purified from the whole bodies of fetal rats with the enzyme from rat brain
Biochem. biophys. Res. Commun.
(1980)
Ha˚kansonR. et al.
Concomitant histochemical demonstration of histamine and catecholamines in enterochromaffin-like cells of gastric mucosa
Life Sci.
(1967)
LjungdahlA˚. et al.
Distribution of substance P-like immunoreactivity in the central nervous system of the rat-I. Cell bodies and nerve terminals
Neuroscience
(1978)
OwenD.A.
Histamine receptors in the cardiovascular system
Gen. Pharmacol.
(1977)
PalaciosJ.M. et al.
The distribution of histamine H₁-receptors in the rat brain: an autoradiographic study
Neuroscience
(1981)
PollardH. et al.
Histidine decar☐ylase and histamine in discrete nuclei of rat hypothalamus and the evidence for mast-cells in the median eminence
Brain Research
(1976)
PollardH. et al.
Histamine and histidine decar☐ylase in brain stem nuclei: distribution and decrease after lesions
Brain Research
(1978)
RaismanG. et al.
Sexual dimorphism in the neuropil of the preoptic area of the rat and its dependence on neonatal androgen
Brain Research
(1973)

TranV.T. et al.

Histidine decar☐ylase: purification from fetal rat liver, immunologic properties, and histochemical localization in brain and stomach

J. biol. Chem.

(1981)

WatanabeT. et al.

Partial purification and characterization ofl-histidine decar☐ylase from fetal rats

Biochem. Pharmacol.

(1979)

WatanabeT. et al.

Evidence for the presence of histaminergic neuron system in the brain: an immunochemical analysis

Neurosci. Lett.

(1983)

WilcoxB.J. et al.

Localization of neuronal histamine in rat brain

Neurosci. Lett.

(1982)

BennetC.T. et al.

Antidiuresis produced by injections of histamine into the cat supraoptic nucleus

Brain Research

(1974)

BleierR. et al.

A cytoarchitectonic atlas of the hypothalamus and hypothalamic third ventricle of the rat

ClineschmidtB.V. et al.

Histamine: intraventricular injection suppresses ingestive behaviour of the cat

Arch. int. Pharmacodyn. Ther.

(1973)

CoonsA.H.

Fluorescent antibody methods

Dahlstro¨mA.

Effect of colchicine on transport of amine storage granules in sympathetic nerves of the rat

Europ. J. Pharmacol.

(1968)

Dahlstro¨mA. et al.

Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons

Acta physiol. scand.

(1964)

DouglasW.W.

Histamine and 5-hydroxytryptamine (serotonin) and their antagonists

FinchL. et al.

Involvement of hypothalamic histamine receptors in the central cardiovasculare actions of histamine

Neuropharmacology

(1976)

GanellinC.R. et al.

Pharmacology of Histamine Receptors

(1982)

GarbargM. et al.

Histaminergic pathway in rat brain evidenced by lesions of the medial forebrain bundle

Science

(1974)

GreenJ.P. et al.

Histamine as a neurotransmitter

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Distribution of the histaminergic neuron system in the central nervous system of rats; a fluorescent immunohistochemical analysis with histidine decar☐ylase as a marker

Abstract

Brain Research

Biochem. biophys. Res. Commun.

Biochem. biophys. Res. Commun.

Life Sci.

Neuroscience

Gen. Pharmacol.

Neuroscience

Brain Research

Brain Research

Brain Research

J. biol. Chem.

Biochem. Pharmacol.

Neurosci. Lett.

Neurosci. Lett.

Antidiuresis produced by injections of histamine into the cat supraoptic nucleus

Brain Research

A cytoarchitectonic atlas of the hypothalamus and hypothalamic third ventricle of the rat

Histamine: intraventricular injection suppresses ingestive behaviour of the cat

Arch. int. Pharmacodyn. Ther.

Fluorescent antibody methods

Effect of colchicine on transport of amine storage granules in sympathetic nerves of the rat

Europ. J. Pharmacol.

Evidence for the existence of monoamine-containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brain stem neurons

Acta physiol. scand.

Histamine and 5-hydroxytryptamine (serotonin) and their antagonists

Involvement of hypothalamic histamine receptors in the central cardiovasculare actions of histamine

Neuropharmacology

Pharmacology of Histamine Receptors

Histaminergic pathway in rat brain evidenced by lesions of the medial forebrain bundle

Science

Histamine as a neurotransmitter