By means of sensitive and specific methods for histochemical and biochemical determination of dopamine (DA), noradrenaline (NA) and 5‐hydroxytryptamine (5‐HT) we have succeeded in demonstrating and mapping out a number of ascending monoamine neuron systems from the lower brain stem by studying the anterograde and retrograde changes that occur in these neurons after various types of brain lesions. In this way it has been possible to discover: 1) a large, uncrossed nigro‐neostriatal DA neuron system; 2) a DA neuron system, arising from cell‐bodies in the mesen‐cephalon, ascending uncrossed in the medial forebrain bundle close to the nigro‐neostriatal DA fibres, and innervating e.g. the tuberculum olfactorium and nuc. accumbens; 3) ascending NA neuron systems with cell‐bodies situated mainly in the medulla oblongata and pons (locus coeruleus, formatio reticularis), and axons running uncrossed mainly in the medial forebrain bundle, innervating e.g. the limbic forebrain structures, the neocortex and the hypothalamus; 4) ascending 5‐HT' neurons with cell‐bodies situated mainly in the raphe nuclei of the mesencephalon (nuc. raphe dorsalis, nuc. raphe medianus), and axons running uncrossed mainly in the medial forebrain bundle, innervating e.g. the limbic forebrain structures and the hypothalamus. The effects observed on the amine levels of the neurons represent intraneuronal and not transsynaptic changes.

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Indirect immunofluorescence histochemistry and receptor autoradiography were used to study the localization of transmitter-/peptide-containing neurons and peptide binding sites in the mediobasal hypothalamus in normal rats and in rats treated neonatally with repeated doses of the neurotoxin monosodium-glutamate (MSG). In the arcuate nucleus, the results showed a virtually complete loss of cell bodies containing immunoreactivity for growth hormone-releasing factor (GRF), galanin (GAL), dynorphin (DYN), enkephalin (ENK), corticotropin-like intermediate peptide (CLIP), neuropeptide Y (NPY), and neuropeptide K (NPK). Tyrosine hydroxylase(TH)-glutamic acid decarboxylase(GAD)-, neurotensin(NT)- and somatostatin(SOM)-immunoreactive (IR) cells were, however, always detected in the ventrally dislocated, dorsomedial division of the arcuate nucleus. In the median eminence, marked decreases in numbers of GAD-, NT-, GAL-, GRF-, DYN-, and ENK-IR fibers were observed. The numbers of TH-, SOM- and NPY-IR fibers were in contrast not or only affected to a very small extent, as revealed with the immunofluorescence technique. Biochemical analysis showed a tendency for MSG to reduce dopamine levels in the median eminence of female rats, whereas no effect was observed in male rats. Autoradiographic studies showed high to moderate NT binding sites, including strong binding over presumably dorsomedial dopamine cells. In MSG-treated rats, there was a marked reduction in GAL binding in the ventromedial nucleus. The findings implicate that most neurons in the ventrolateral and ventromedial arcuate nucleus are sensitive to the toxic effects of MSG, whereas a subpopulation of cells in the dorsomedial division of the arcuate nucleus, including dopamine neurons, are not susceptible to MSG-neurotoxicity. The results indicate, moreover that the very dense TH-IR fiber network in the median eminence predominantly arises from the dorsomedial TH-IR arcuate cells, whereas the GAD-, NT-, GAL-, GRF- and DYN-IR fibers in the median eminence to a large extent arise from the ventrolateral arcuate nucleus. Some ENK- and NPK-positive cells in the arcuate nucleus seem to project to the lateral palisade zone of the median eminence, but most of the ENK-IR fibers in the median eminence, located in the medial palisade zone, seem to primarily originate from an area(s) located outside the arcuate nucleus, presumably the paraventricular nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

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Dopamine (5 to 50 mug) applied bilaterally to the nucleus accumbens of reserpine-nialamide pretreated rats produced a marked dose-dependent rise in coordinated locomotor activity, devoid of stereotypies such as gnawing, rearing and licking seen after dopamine application (50 mug) to the neostriatum. The locomotor activity was completely blocked by pimozide, but not by phenoxybenzamine. The effects of apomorphine or d-noradrenaline was similar to those of dopamine. In contrast, l-noradrenaline produced a "convulsive" syndrome devoid of coordinated locomotor activity, and this convulsive syndrome could be completely blocked by phenoxybenzamine but not by pimozide. Release of endogenous dopamine by d- or l-amphetamine (10 and 50 mug) in the nucleus accumbens produced a rise in coordinated activity, the d-isomer was about 4 times as potent as the l-isomer, and the effect of the d-isomer was blocked completely by alpha-methyltyrosine. Bilateral application of trifluoperazine (2.5 mug) to the nucleus accumbens completely blocked the effect of systemically administered d-amphetamine (1.5 and 3.0 mg/kg), but similar application to the area of the central nucleus of the amygdala or the neostriatum was much less effective. Partial protection of the endogenous dopamine stores against the depleting action of reserpine by local application of metatyramine to the nucleus accumbens resulted in a higher level of basal activity than in control animals. Application of dopamine or noradrenaline to the area of the central nucleus of the amygdala or to the olfactory tubercles did not lead to any consistent changes in locomotor activity. The nucleus accumbens and olfactory tubercles contained most of the dopamine in the limbic forebrain, with noradrenaline more evenly distributed. These data suggest that the nucleus accumbens plays an important role in the locomotor activity in rats.

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ANDBN, N.-E., K. FUXE, B. HAMBERGER and T. HOKFELT. A quantitatiue study on the nigro-neostriatal dopamine neuron system in the rat. Acta physiol. scand. 1966. 67. 306-3 12.In a combined biochemical and histochemical investigation the following quantitative data on a unilateral nigro-neostriatal dopamine neuron system in the rat have been obtained or calculated. -The number of neurons is 3,500 on the average. -There are about 130 pg dopamine per neuron ( I pg = lo-'* 9). -The terminals contain 50 (or 150) times more dopamine than the cell bodies. -The terminal system of one neuron varies mainly between 55 and 77 cm in length and contains about 500,000 varicosities. -The neostriatum, with a volume of 33 mm*, contains loB dopamine varicosities occupying 0.3 yo of the volume, and 4,000,000 nerve cell bodies (not containing dopamine). -One average dopamine varicosity, with a diameter of 0.4 p , contains 2.5 x lo-' pg dopamine, and has a doparnine concentration around 8,000 pg/g. -O n e dopamine cell body of the substantia nigra, with a mean diameter of 30 p , contains 2.5 (or 0.8) pg dopamine, and has a dopamine concentration around 200 (or 60) pg/g.