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The intracellular pH (pHi) of neurons is tightly regulated, mainly by membrane-bound transporters acting as acid extruders or acid loaders. Regulation of pHi helps to control neuronal excitability, as increased bioelectric activity moderately lowers pHi and, in the sense of a negative feedback loop, intracellular acidosis mostly reduces neuronal excitability. Moreover, a change of pHi widely influences complex cellular functions. With respect to neuropsychopharmaca, little is known about whether or not they may affect neuronal H ( + )-homeostasis. To this aim, we tested several antipsychotics, antidepressants, anticonvulsants, and lithium for effects on neuronal pHi, using guinea pig hippocampal slice preparations in which CA 3 pyramidal neurons were loaded with the pHi-sensitive dye BCECF-AM. All antipsychotics, most antidepressants and about half of the anticonvulsants tested so far elicited reversible changes of neuronal pHi when applied at therapeutic and supratherapeutic concentrations. Although these results await confirmatory in vivo experiments, we believe that the pHi activity of neuropsychopharmaca needs further attention, especially when therapeutic mechanisms or even harmful side effects are discussed., (© Georg Thieme Verlag KG Stuttgart · New York.)

Statins, i.e. HMG-CoA reductase inhibitors, reduce the risk of stroke and may have therapeutic potential for other neurologic diseases, including multiple sclerosis and Alzheimer's disease. In addition to lowering cholesterol levels, statins exert a number of cholesterol-independent (pleiotropic) effects. While endothelial, anti-thrombotic, anti-inflammatory, and immunomodulatory, i.e. peripheral, effects of statins are well known, little is known about the direct effects on neurons. This may be of clinical relevance because some statins are able to cross the blood-brain barrier. Recent experimental studies demonstrate that statins reduce the activity of neuronal glutamate receptors and protect neurons from excitotoxic insults. At higher doses, however, statins may also inhibit neurite sprouting and even induce neuronal apoptosis.

Acetylcholine (ACh) is a prototypical neurotransmitter that has recently been recognized to occur extraneuronally in a large variety of cells. ACh and its nicotinic and muscarinic receptors are produced in the epidermis and in the adnexal structures of the skin in a highly complicated pattern. They are also produced in melanocytes, fibroblasts, endothelial cells and immune cells. Through autocrine, paracrine and endocrine mechanisms, the cholinergic system is involved in the basic functions of the skin, such as keratinocyte differentiation, epidermal barrier formation, sweating, sebum production, blood circulation, angiogenesis and a variety of immune reactions. Hence diseases like acne vulgaris, vitiligo, psoriasis, pemphigus vulgaris and atopic dermatitis may be influenced. The exploration of the extraneuronal cholinergic system of the skin has only just begun.

Pedophilia is a complex bio-psycho-social disorder often associated with serious offending. Knowledge about neurobiological correlates that could serve as diagnostic and maybe even as prognostic markers is limited. FMRI examination, which shows neuronal activation in vivo and therefore represents a neurobiological correlate, was not done in pedophilia so far. We report on results of an fMRI examination in a homosexual pedophilic sex offender who differed significantly in neuronal activation during exposure to arousing visual material (young boys in underwear) from normal controls. In self assessment on a visual analogous scale the pedophilic offender scored the pictures of the boys as not being interesting and sexually not stimulating. Nevertheless presentation of the pictures of the boys resulted in the pedophilic offender in a significant activation of the attention network and the right orbitofrontal cortex. In contrast to the controls there was no activation of left hemispheric areas relevant for speech. The study design will be continued in a larger sample to examine whether there is a possible neurobiological correlate of pedophilia which can be changed by therapeutic interventions.

The spectrum of action of flupirtine includes analgesic, muscle-relaxant and neuroprotective properties. The substance's mechanism of action has yet to be fully explained. Over the past few years, however, evidence has accumulated that flupirtine interacts with the glutamatergic N-Methyl-D-Aspartate (NMDA) receptor. Although it was not possible to demonstrate a direct effect on the NMDA receptor, all of the findings pointed to an indirect influence on the NMDA receptor in the sense of a functional NMDA antagonism. It was thus postulated that a site of action "up- or downstream" of the NMDA receptor is influenced. Such a site of action proved to be the G-protein-activated inwardly rectifying K+ channels (GIRK), the opening of which leads to a stabilization of the resting membrane potential of neuronal cells and thus causes an indirect inhibition of the NMDA receptor. At therapeutically relevant concentrations, flupirtine is a neuronal potassium channel opener. This mechanism may explain the spectrum of action of flupirtine. Selective neuronal potassium channel opening (SNEPCO) thus proves to be a new principle of action, making flupirtine the prototype of a new substance class with analgesic, muscle-relaxant and neuroprotective properties. The experimental basis for this working hypothesis and the resulting model concepts are presented from the perspective of a four-stage approach.

Introduction: There is no data available on the action of etomidate on ion currents in human neuronal cells. Therefore the effects of etomidate on a human neuronal delayed rectifier potassium current were investigated., Method: Outward rectifying potassium currents of human neuroblastoma SH-SY5Y cells were measured using the whole cell patch-clamp technique. Cells were grown in RPMI-medium (+Pen/Strep and FCS) at 37 degrees C and 5% CO2. The holding potential was -80 mV. Potassium currents were evoked by depolarizing the membrane potential to values from -50 mV to +90 mV in 10 mV steps using an EPC-7 patch-clamp amplifier (List medical electronics) and pclamp version 5.71 (Axon instruments)., Results: Etomidate differentially inhibited steady-state and peak potassium current with IC50-values of 170 microM for peak current suppression and 120 microM for steady-state current respectively. Etomidate induced inactivation-like behaviour of the potassium current and changed the voltage dependence of potassium current activation., Conclusion: The results demonstrate that etomidate has more than one effect on the potassium current, indicating the complexity of general anaesthetic actions on neuronal targets. The actions of etomidate on human neuronal potassium currents may potentially contribute to the myocloni observed with this general anaesthetic agent during induction of anaesthesia.

The cascade of pathobiochemical reactions caused by cerebral ischemia is complex and not completely understood. One important factor seems to be the disturbed calcium homeostasis. Measurement of cytosolic-free Ca2+ concentration [Ca2+]i is possible with the Ca(2+)-sensitive dye fura-2. Using this technique it can be investigated if, and how, neuroprotective drugs influence the cellular calcium homeostasis. In hippocampal neurons K+ or glutamate, added to the buffer solution, evoked elevations of [Ca2+]i in a concentration-dependent manner. We demonstrated that the calcium antagonist nimodipine or the non-competitive NMDA receptor antagonist dizocilpine added to the buffer solution could inhibit concentration-dependently the elevation of [Ca2+]i. The measurement of [Ca2+]i can be used for studies on the mechanism of action as well as for screening purposes of neuroprotective drugs.

An adequate number of nerve cells, their connection by dendrites and axons, the transmission of information by chemical mediators are all necessary for normal brain function. Monocarbonic acid residues, purines and pyrimidines and tubulins and biopterin are essential to ensure that the necessary chemical processes can take place. In trisomy 21 the metabolism is disturbed by the enhancement of individual enzyme activities. Particular clinical effects suggest specific therapeutic interventions. The effects can be influenced by way of the monocarbonic acid metabolisms. The action of thyroxine is especially interesting, as it inhibits the disintegration of monocarbonic acids.

We recently demonstrated that the net accumulation of 3H-norepinephrine in the rat pheochromocytoma cell line PC12 was reduced by anesthetic concentrations of n-alkanols and the volatile anesthetics halothane, enflurane, isoflurane, and methoxyflurane. In PC12 cells, as in adrenergic neurons, norepinephrine is transported across the plasma membrane by a saturable, high-affinity, carrier-mediated mechanism (uptake1), which follows Michaelis-Menten kinetics, is energy- and sodium-dependent, and is inhibited by low concentrations of cocaine and the tricyclic antidepressant desipramine. Although uptake1 is the most important process for the removal of norepinephrine from the synaptic cleft, the net accumulation of norepinephrine within the neuron also depends on other factors including its vesicular uptake and storage within the granules, its metabolism by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT), and the efflux of its more lipophilic metabolites. In our previous report we could not exclude the contribution of any of these factors to the observed inhibitory effects of volatile substances. Therefore, the aim of the present study with ethanol and methoxyflurane was: (1) to elucidate further the exact mechanism responsible for the reduction of the norepinephrine accumulation; and (2) to investigate the anesthetics' interaction with the substrate recognition site, which is identical with the desipramine binding site on the norepinephrine carrier. METHODS. For 3H-norepinephrine uptake experiments, PC12 cells were cultured on dishes (60 mm, Nunc) coated with polyornithine. Reserpine (10 microM) was added to the culture 24 h before the experiment to deplete endogenous norepinephrine. The initial carrier-mediated transport rate (60 s) was measured as previously described. 3H-desipramine equilibrium binding was determined with isolated plasma membranes prepared from PC12 cells grown in suspension culture. The carrier-mediated uptake of 3H-norepinephrine and the specific 3H-desipramine binding were defined as those inhibited by 1 microM nisoxetine. All buffers contained 10 microM pargyline and 10 microM U-0521 to inhibit MAO and COMT. Incubations were done in the presence and absence of methoxyflurane (1% and 2% vol/vol in synthetic air containing 5% CO2) or ethanol (5% vol/vol). Media had been equilibrated with methoxyflurane by bubbling (30 min) and were routinely checked by gas chromatography. RESULTS AND DISCUSSION. Methoxyflurane and ethanol inhibited uptake1. However, reduction of uptake1 was far less pronounced than that previously found for the net accumulation of norepinephrine. Even at a vaporous concentration of 2% (corresponding with an over 15-fold half-maximal inhibitory concentration for norepinephrine accumulation), methoxyflurane produced only 58% inhibition of the high-affinity uptake...

Effects of Aminobenzoic Acid Derivatives on the Ionic Currents in Myelinated Nerve/1st Communication: Dose-response curves Derivatives of aminobenzoic acid were modified and their blocking potencies on the ionic currents of single potential clamped myelinated nerve fibres were tested by means of dose-response curves. Starting from metacaine (ethyl m-aminobenzoate), derivatives of different basicity were produced by N-dimethylization, N-quarternization and by preparing a corresponding aliphatic amine. The corresponding free acids and the structural isomers of metacaine were tested as well. The physico-chemical properties of the derivatives were characterized by their pKa-values and their octanol/water partition coefficients. Our findings suggest that the site of action of the aminobenzoic acids tested is located at the inside of the nerve membrane. Moreover, no indications of binding to a receptor in a pharmacological sense were found.

Neuronal membranes of postsynaptic origin twofold enriched in acetylcholinesterase, muscarinic acetylcholinereceptor and (Na+/K+)-ATP-Phosphohydrolase, proteins associated with cholinergic nerve excitability, were prepared with yields between 60 and 75% from bovine caudate nucleus. On subfractionation of these membranes an additional twofold enrichment of the mentioned proteins is achieved in different subfractions. SDS-gradient gel electrophoresis shows that these subfractions have slightly different polypeptide compositions. Neuronal membranes of presynaptic origin on the other hand, prepared from purified synaptosomes, possess only small amounts of the mentioned proteins, showing no enrichment with respect to the homogenate. Solubilization of acetylcholinesterase with 1 M NaC1 as well as of muscarinic acetylcholinreceptor with 2 M NaC1 does not succeed. These proteins are therefore not solely bound by ionic forces to the isolated membranes from bovine caudate nucleus.

Research in molecular neurobiology has recently entered a new phase of rapid development as a result of the application of the techniques of molecular genetics. This is illustrated by recent work on the electric ray (Torpedo marmorata and T. californica), whose electric organ is a rich source of cholinergic synapses. Other examples from recent literature of the application of the recombinant DNA technique to the mammalian central nervous system are given and possible future developments are discussed.

Permeability of the blood-brain barrier is restricted with respect to amino acids involved in neurotransmission. This finding is well-documented in the case of gamma-amino-butyric acid (GABA) and glycine. Aspartic acid, which is also considered to be a transmitter, equally does not cross the blood-brain barrier in the rat with ease. This amino acid is also thought to be a transmitter in the retina. In order to examine the permeability of the blood-retina barrier with respect to aspartic acid, and investigation was undertaken of the effect of asparate on the light-induced sum potential of the retina in the isolated, perfused cat eyeball, a preparation which guarantees intact retinal circulation. The findings were compared with findings in the isolated retina where the substance was brought into direct contact with the retinal neurons. It was found that aspartate crossed the vascular barrier only to a limited extent and with delay. These results support the hypothesis that aspartic acid is involved in the retinal information processing.

The entorhinal afferences to Fascia dentata and Stratum lacunoso-moleculare of CA1 could be visualised by means of anterograde axoplasmic transport 5 days after L-[5-3H]-proline injection into the entorhinal cortex. Furthermore, the macromolecule-bound tracer was found in the perikarya of granule cells and mossy fibres as well as in the cell bodies of the CA1 pyramids. These findings indicate that labelled material, released from the axonal terminals of the perforant pathway, is taken up by these neurons.

The simultaneous demonstration of 3H-radioactivity and "light" and "dark" neurons by histological staining revealed that the occurrence of "light" and "dark" neurons are morphological correlates of different activity stages of cell metabolism. In this connection it became evident that "light" nerve cells incorporated significantly greater amounts of fucose and therefore should be regarded as metabolically more active. We also present evidence that "dark" neurons are not artificial products caused by postmortem trauma to the brain inadequately fixed (as pointed out by Cammermeyer).

1. GABA was demonstrated in rat brain in fluorescence histochemistry. The alteration by application of submaximal doses of drugs of the distribution and intensity of the transmitter fluorescence was studied in hippocampus and cerebellum. 2. Isonicotinic acid hydrazide and Penicillamine leads to a distinct grain formation and diminishing of the fluorescence product, normally appearing homogenous. These effects are considered to reflect an enzyme (GAD) inhibition. 3. By Cycloserine a distinct increase of the GABA fluorescence is effected, presumably by inhibiting GABA-transaminase-activity. 4. Chloropromazine causes diminishing, grain formation and dislocation as well of the fluorescent product, supposedly due to an affection of the membrane binding properties of GABA. 5. Hypotheses concerning the chemical events of the GABA-reaction are worded.

Cerebrocortex of the neonatal rats were cultivated (--14 days). The cultures were studied living and with histological and fluorescence histochemical methods. A differentiation of neuronal cell- and fiber elements, oligodendro glial cells and astrocytes was found. The glyoxylic acid technique to estimate biogenic monoamines (Lindvall et al. 1974) was adapted up the cultivated explants. The normal cultures have only 24 h post cultivationem a specific fluorescence granularly in small concentration of the surface of the explant and in the explant self. Incubations with noradrenaline and dopamine demonstrated a various accumulation of the exogenous transmitters in the various parts of the cultivated explants. Uptake and releasing mechanisms in the cultivated material of the cerebrocortex were discussed with respect to the results of the sympathetic ganglia in vitro.

Three batches of senile guinea pigs were injected i.m. daily with 80 mg/kg, 50 mg/kg, or 30 mg/kg up to 10 weeks. With the dosage employed neurons of the central nervous system showed in all animals a significant reduction of lipofuscin pigment. A characteristic type of vacuolisation of the pigment is a preliminary sign of its reduction in size and quantity. Residuals of lipofuscin can be detected in astrocytes and in greater quantity in microglia cells and cells of the capillary wall. The dissolution of lipofuscin is not only found in the CNS but also in the myocardium and in the liver. In the latter organs the removal of pigment is carried out by phagocytes towards capillaries. The actual uptake of phagocytes is believed to occur by the process of exocytosis and pinocytosis. A destruction or an invasion of neurons by microglia has not been observed. Lipofuscin removal at a very small rate by microglia cells appears to occur normally in the ageing animal, but is greatly enhanced by centrophenoxin. Cessation of drug application does not stop the process of removal at once and the process continues as far as we can judge by our experiments for several weeks without further drug application. Even 30 mg/kg per day were found to be sufficient to initiate and sustain lipofuscin removal.

Nerve cells with their very long axons and dendrites have an effective system of anterograde and retrograde transport. In the retrograde direction there is, in addition to endogeneous cell constituents, a substantial transport of exogenous material like e.g. trophic factors like NGF. We have found that molecules which bind with high affinity to receptors in the nerve teminal surface membranes (e.g. NGF, tetanus and cholera toxin, lectins) are selectively internalized and transported retrogrdely to the cell body. Although most of them are incorporated into lysosomes in the cell body, they can nevertheless exert specific signal functions in the cell (NGF). Tetanus toxin, however, is released by the dendrites and transferred trans-synaptically to higher order neurons. We suggest that this retrograde and trans-synaptic transport represents an important pathway for "trophic" signal molekules, which convey information from the target cells to the innervating neurons. The same pathways can be used by neurotoxins *tetanus toxin) and neurotrophic viruses for entering the nervous system.

Effects of Aminobenzoic Acid Derivatives on the Ionic Currents in Myelinated Nerve/2nd Communication: Sodium inactivation. Derivatives of aminobenzoic acid similar to metacaine were modified and their effects on the sodium inactivation and on the sodium permeability constant, PNa, of single potential clamped myelinated nerve fibres were tested. Comparing the observed shift of the inactivation curves and the reduction of PNa with the octanol/water partition coefficients of the drugs tested, a minimum lipid solubility seems to be necessary for the substances being efficacious. It is assumed that the uncharged aminobenzoic acids reduce PNa by disturbing the lipid matrix in an unspecific manner. The observed shift of the inactivation curves is explained in terms of the fixed charges at the inside of the membrane being moved apart by the uncharged compounds thus lowering the effective membrane potential. Moreover, no indications for a receptor-mediated mechanism were found.

Endorphins are peptides with opiate-like action synthesized in various tissue, e.g. in intestine and central nervous system. Exact characterization of opioid-specific receptors and sensitive biological test assays for opioids were prerequisites for the discovery of these substances. Met- and leu-enkephalin were the first endorphins discovered. Both are pentapeptides. One of them, namely met-enkephalin (H-Tyr-Gly-Gyl-Phe-Met-OH) is likely to be a fragment of the peptides alpha- and beta-endorphin, both showing opioid-like actions, as well as of beta-lipotropin, a polypeptide showing no opioid-like activity: all these peptides include the pentapeptide met-enkephalin within their molecules. beta-liportropin and ACTH are likely to be fragments of a common precursor. At least both enkephalins (which are studied better as yet than the other endorphins) are supposed to be formed in the soma of the neuron and transported to the nerve ending, where they are released. They seem to have the function of neuromodulator or even of neurotransmitters. The pharmacological actions of endorphins resemble those of "classical opiates", both having e.g. analgesic effects. Both enkephalins are, among various other brain and spinal cord areas, localized in those areas which seem to be of particular relevance for perception and transmission of pain. They might, under certain conditions, play some part in the regulation of pain perception. Furthermore, they seem to be relevant for some neuroendocrine processes. Their relevance in symptoms of schizophrenic psychoses seems to be more doubtful. In opiate dependence no significant alterations of endorphin concentrations could be observed as yet.

The term neurohumoral transmission designates the transfer of a nerve impulse from a presynaptic to a postsynaptic neuron by means of a humoral agent e.g. a biogenic amine, an amino acid or a peptide. This process involves several steps, i.e. biosynthesis, storage, release, receptor interaction and inactivation of the transmitter. A neuromodulator modifies, for instance the release of a transmitter by action on a presynaptic transmitter neuron. Biogenic amines may also be released from non-synaptic nerve terminals and possibly exert a modulatory effect on other neurons. The regulation of the transmitter dynamics at the enzymatic level occurs by end-product inhibition and by enzyme induction. In addition, there are regulatory mechanisms originating from autoreceptors and postsynaptic receptors which operate via feedback action. Stimulation or inhibition of receptors may lead to receptor sub- and supersensitivity respectively. Numerous neuro-psychotropic drugs used in medical practice act on the various steps of neurohumoral transmission and thereby influence the dynamics of neurotransmitters and modulators.

The Regio frontalis posterior of the motor cortex of adult rats was investigated by means of the fluorescence-PAS-reaction. Using various Schiff-type-reagents - substituted with acriflavine, rhodamine B, rhodamine 6G, safranine T - a fluorescent reaction product has been found in different amounts in the pyramidal neurons and in other cellular elements. After application of acriflavine different degrees of PAS-reactivity could be demonstrated in various cortices. Dexamethasone affected an increase of the fluorescent reaction product in individual pyramidal neurons. Ideas on the possible reaction mechanism after application of various Schiff-type-reagents have been proposed.

There are no qualitative differences in the electrophoretic patterns of histones from neurones and glia. A 25% increased acetylation rate is found in neuronal histones as compared to glial histones after incubation of chopped brain in a [14C]-acetate containing medium. This result probably reflects different condensation states of the chromatins of both cell types, as demonstrated by electron microscopy.

Metachromatic leucodystrophies (MLD) comprise a small group of heredodegenerative disorders of the nervous system. Deficiency of sulfatide-sulfatase or arylsulfatase A is the common defect in all forms of MLD leading to lysosomal sulfatide storage in the nervous tissue and in the kidney. On the basis of animal experiments, experiments with cultured fibroblasts of the patients as well as ultrastructural studies in a case of prenatal MLD, the following pathomechanism is proposed: 1. Lysosomal degradation of a large portion newly synthetised sulfatide normally regulating the net synthesis and incorporation of sulfatide into myelin, causes early accumulation of sulfatide in lysosomes of myelinating cells and in neurons in the genetic deficiency of arylsulfatase A. 2. Early accumulation of sulfatide does not lead to disturbance in myelination. Demyelination occurs possibly by storage of a cytotoxic compound, psychosin sulfate, also a substrate for the missing enzyme. Prevention of MLD is possible by prenatal diagnosis of arylsulfatase A deficiency in cultured amniotic cells. Enzyme substitution of the missing arylsulfatase A is possible by exogenous uptake of the enzyme in cultured fibroblasts. Thereby the defect of sulfatide degradation can be corrected. Although principles of enzyme substitution have been demonstrated, the problems of treating patients with MLD with arylsulfatase A infusions have yet to be overcome.

Peptides with morphine-like efficacy, which are called endorphines and enkephalines, are formed by the nerve cells of numerous segments of the central nervous system and of the gastrointestinal canal. The efficacy of these peptides which decrease the sensation of pain is increased in certain stress (lesions, operative interventions, heat, birth). They stimulate the activity of the sympathetic nervous system, influence the secretion of certain hormones and decrease the sensitivity to pain. In acupuncture the release of the endorphines is increased. The formation of the endorphines takes place by peptidolysis from a prodromal molecule--the pro-opiomelanocortin--and the formation of the enkephalines by peptidolysis from the proenkephalines. The binding of the endorphines and of the enkephalines takes place on receptors in the area of the synapses of the certain nerve cells, which also bind opium alkaloids. Under the influence of the opiate-receptor-complexes an influence on the stimulus conduction takes place which is reduced. Particularly those nerve cells are concerned which conduct stimulations from nozireceptors. The endogenic opiates take furthermore part in the regulation of reproduction, the body temperature, the respiration and the function of the gastrointestinal canal.

The lipofuscin contents in pyramidal cells of laminae III and V in area 10 (Brodmann) of the frontal brain from 6 men who recently died at different ages without any neurological or psychiatric symptoms were investigated by electronmicroscopic-morphometric methods. The results of this investigation actually do reveal an increase of the lipofuscin with age, but also demonstrate to what extent this process is subject to individual variability. Great differences in the accumulation of the lipofuscin exist among the cells within the same cytoarchitectonic layer. On the other hand wide correspondence between the mean values of both laminae can be stated.

A short review is given on the effects of antidepressant drugs (tricyclic thymoleptics and MAO inhibitors), neuroleptics and lithium salts on catecholamine and serotonin metabolisms in brain. The second part deals with some pharmacokinetic investigations with these psychotropic drugs. In connection with tricyclic thymoleptics some factors influencing steady-state plasma concentration and their relation to the therapeutic effect are discussed. Furthermore, recent investigations into the pharmacokinetics of lithium salts are dealt with.

The serotonergic neurons of the nucleus raphe dorsalis (NRD) of the adult male Wistar rat were characterized morphologically using Nissl and Golgi-Kopsch techniques, fluorescence histochemistry as well as a peroxidase-antiperoxidase (PAP) immunocytochemical method employing specific antibodies to serotonin. 1. The numerous serotonin-positive neurons within (and around) the NRD exhibit--in agreement with data of the literature--characteristic heterogeneous distribution patterns both in rostro-caudal direction and also dorsoventral particularly in the mesencephalic part, the zone of the largest extension of the nucleus. Several groups with high cell concentration could be divided. The neurons differ in their immunoreactivity. 2. Based on different criteria, especially the number and arrangement of dendrites as well as the cell shape, three types of serotonergic neurons could be identified: multipolar, fusiform (bipolar) and small ovoid ones. A parallel analysis in Golgi-stained material offers the possibility for more detailed studies and further characterization. 3. With respect to functional interpretations some morphological peculiarities seem to be remarkable, e.g. the close relation between several neurons, the tight dendritic contact to many blood vessels or the formation of a dense serotonin-positive fiber plexus along the floor of the aqueductus and fourth ventricle. Studies, following stereotactic application of the neurotoxin 5.7-dihydroxytryptamine into the NRD, show furthermore that the majority of serotonergic neurons--independently of the cell type--reveals signs of cell degeneration. The findings presented confirm previous studies and should provide also further insights into the morphology of the 5-HT neurons of rat NRD as well as for the explanation of functional aspects.