J.P. Herman

Noradrenergic innervation of the rat hypothalamus: Experimental biochemical and electron microscopic studies

The concentrations of noradrenaline in individual hypothalamic nuclei and in the median eminence were measured 7-10 days following surgical transections of the lower brain stem or electrolytic lesions of the medullary noradrenaline-containing cell groups. Terminal degeneration in the hypothalamus was studied after the same surgical procedures. Direct, monosynaptic connections between the dorsomedial hypothalamic nucleus and all the noradrenaline-containing cell groups investigated were found. Degenerated synaptic boutons were demonstrated in the median eminence, arcuate, dorsomedial, ventromedial, periventricular and paraventricular nuclei following lesions of the solitary tract and of the lateral reticular nucleus. Biochemical measurements indicate that the pontine-medullary noradrenergic cell groups are the source of hypothalamic norepinephrine. Ascending noradrenergic fibers destined to terminate in the hypothalamus are provided by several cell groups, though the bulk of the NA-fibers seem to originate in the A1-group, in the ventrolateral part of the medullary reticular formation. Most of these fibers join the ventral NA bundle, fewer join the dorsal periventricular tract and several probably also join the dorsal NA bundle. A significant overlap was found in the hypothalamic arborization of the noradrenergic fibers, so that no strict topographical organization seems to be present either in their origin or their termination.

Simultaneous radioenzymatic assay of catecholamines and dihydroxy-phenylacetic acid /DOPAC/; comparison of the effects of drugs on the tuberoinfundibular and striatal dopamine metabolism and on plasma prolactin level

Abstract A simultaneous radioenzymatic assay for catecholamines and DOPAC has been developed. 3 H-Methoxy amines and 3 H-homovanillic acid formed in the presence of 3 H-S-adenosyl-methionine and catechol-O-methyl transferase were separated by organic solvent extraction and chromatography. Chlorpromazine, haloperidol, but not sulpiride increased the DOPAC content in the striatum, without affecting the DOPAC level in the median eminence. γ-Butyrolactone increased the dopamine content also only in the striatum. The monoamine oxidase inhibitor pargyline decreased the DOPAC level in both areas examined. All the substances employed increased plasma prolactin level. The biochemical responses of nigrostriatal and tubero-infundibular dopaminergic neurons may not be analogous.

Adrenergic innervation of the rat hypothalamus

The adrenergic innervation of the hypothalamus was studied by measuring hypothalamic adrenaline levels following surgical transection of the lower brain stem or electrolytic lesion of the medullary adrenaline-containing cell groups. The adrenaline levels in some hypothalamic nuclei and in the median eminence showed a slight decrease after partial transection of the medulla oblongata, whilst there was a pronounced decrease (by 59-78%) 7-10 days following total hemisection or unilateral lesion of the C1-catecholaminergic cell group in the medulla oblongata.

Total and partial hypothalamic deafferentations for topographical identification of catecholaminergic innervations of certain preoptic and hypothalamic nuclei

After total deafferentation of the medial hypothalamus in the rat, noradrenaline concentration in the nucleus arcuatus and the eminentia mediana diminished to one-third. The same decrease of noradrenaline concentration resulted also from partial (anterolateral) deafferentation. Rostral and caudal cuts from the medial hypothalamus did not induce any change in the noradrenaline concentration of the two above-mentioned areas. This indicates that noradrenaline containing axons enter the medial basal hypothalamus laterally from the medial forebrain bundle. Total or partial deafferentation of themedial hypothalamus did not affect noradrenaline or dopamine concentrations in the nucleus preopticus medialis, the nucleus interstitialis striae terminalis, the nucleus hypothalamicus anterior and nucleus supraopticus. The catecholaminergic fibres supplying these regions do not pass the medial hypothalamus, but probably ascend laterally from it, in the medial forebrain bundle. The noradrenaline innervation of the nucleus dorsomedialis takes its origin in the ventral noradrenaline bundle and the fibres from the medial forebrain bundle ascend into the nucleus from the lateral side. After total or lateral deafferentation of the medial hypothalamus, that ransects the fibres running to the nucleus laterally, noradrenaline concentration decreases, apart from the nucleus located within or outside the deafferented island. In this case anterior or posterior deafferentation of the hypothalamus is ineffective. Total deafferentation did not change dopamine concentration in the nuclei of the medial basal hypothalamus, thereby furnishing evidence for its intrahypothalamic origin from the A12 cell group. However, after total deafferentation, some slight decrease of dopamine concentration could be observed in the median eminence. This suggests that the dopamine concentration in the median eminence does not originate exclusively from thenucleus arcuatus but to some extent originates from extrahypothalamic sites. After posterior deafferentation, which destroys the fibres of the incertohypothalamic dopamine system, dopamine concentration in the nucleus dorsomedialis decreases. After total deafferentation of the medial hypothalamus, which isolates the nucleus from the ventral nuclei (and so also from the A12 cell group) of the medial hypothalamus, the dopamine concentration in the nucleus dorsomedialis did not change.

Dopamine, noradrenaline and 3,4-dihydroxyphenylacetic acid (DOPAC) levels of individual brain nuclei, effects of haloperidol and pargyline

Noradrenaline (NA), dopamine (DA) and DOPAC were determined with a newly developed radioenzymatic method simultaneously in the striatum, limbic system, hypothalamus and in catecholamine-containing cell groups of the rat brain. Only a loose relationship could be established between DOPAC and DA contents in the various brain areas. The lowest relative DOPAC level (DOPAC/DA ratio) was found in the median eminence, while it was the highest in the periventricular nucleus of the hypothalamus. Haloperidol increased the DOPAC level in only part of the nuclei examined (striatum, olfactory tubercle, central amygdaloid nucleus), while in other limbic regions as well as in the hypothalamic dorsomedial, arcuate and paraventricular nuclei it proved to be ineffective. The DOPAC level in the locus coeruleus was decreased by haloperidol. Pargyline caused an appr. 50% decrease of DOPAC content of most of the nuclei in 10 min; the effectivity of the drug did not show parallelism with that of haloperidol. The monoamine oxidase inhibition caused no change in the DOPAC level in the hypothalamic periventricular and paraventricular nuclei. Results are discussed as a consequence of different reactivity of various DA-ergic terminals and catecholamine cell bodies to haloperidol and pargyline.

Catecholamine concentration of various brain nuclei of the rat as affected by ACTH and corticosterone.

The acute effect of ACTH and corticosterone on catecholamine concentration of individual brain nuclei has been examined. ACTH significantly increased the noradrenaline (NA) content in the locus coeruleus, and decreased it in the ventromedial and arcuate nuclei. No change was observed after ACTH in the dopamine (DA) concentrations of the mentioned areas and in the catecholamine level of the mamillary body, hippocampus, medial habenular nucleus and of the pituitary. Corticosterone increased the NA content of the supraoptic nucleus and the NA and DA levels in the median eminence, while it did not affect the amine concentrations in the locus coeruleus.

ACTH INDUCED CHANGES IN THE TRANSMITTERAMINE CONCENTRATION OF INDIVIDUAL BRAIN NUCLEI OF THE RAT

Publisher Summary The changes of noradrenaline (NA) and serotonin (5HT) metabolism in the brain as induced by various forms of stress have been shown. These studies were designed to study the effect of environmental influences on the metabolism of amines in the central nervous system. Assuming that the rapid responses of the adrenocortical system might be reflected in changes of transmitter level in individual nuclei, the present study demonstrates whether there are changes in amine concentration, induced by acute hormonal treatment, in specific synaptic areas of the brain. The effect of adrenocorticotropic hormone (ACTH) that is observed might be direct and/or corticosterone-mediated. Structures that are responsible for the regulation of the corticotrophin releasing factor (CRF)-ACTH release cannot be determined by the methods applied, However, it might be suggested that the serotoninergic and catecholaminergic synapses, playing a role in this regulation, are present in the nuclei in which transmitter amine content is influenced by ACTH: the arcuate and in the medial, mamillary nucleus.

Electrical stimulation of the median eminence in rats, changes in catecholamine content and in plasma prolactin and growth hormone concentrations

Abstract Effects of field stimulation of the medial basal hypothalamus (MBH) and coaxial stimulation of the median eminence was studied on the catecholamine and DOPAC levels of the median eminence and on the prolactin and growth hormone release. The field stimulation induced an increased prolactin and growth hormone secretion without altering the catecholamine and DOPAC level. The direct electrical stimulation of the median eminence reduced the noradrenaline and dopamine content without significant changes in DOPAC concentration and in hormone secretions. It is concluded that (1) variations of DOPAC content are inadequate indicators of neuronal activity in the median eminence; (2) the multiple interaction of the stimulated neurons in the median eminence may mask the expected biochemical and hormonal responses to electrical stimulation.