Serotonin neurons in the rostral and caudal brainstem raphe nuclear groups give rise to collateralized ascending and descending projections which provide modulatory input into most networks throughout the entire neuraxis. The rostral raphe system is interconnected with target forebrain areas through reciprocal limbic-midbrain loops, which suggests that serotonin has a role in the regulation of complex intelligent adaptive behavior. Serotonergic pathways sensitize brainstem and spinal cord central rhythmic pattern generators which organize repetitive autonomic and motor activities, e.g. oral-buccal and nutritive behaviors, facilitate tonically active motor neurons innervating antigravity muscles, and disfacilitate somatosensory information processing. Serotonin effects are mediated by multiple receptor subtypes with distinct pre- and postsynaptic localization and regional distribution pattern. They belong to the G protein superfamily, coupling to adenylate cyclase (5-HT1,4,5,6,7) or phospholipase C (5-HT2), and to the ligand-gated ion channel superfamily (5-HT3). Drugs acting at these receptors are known to modulate various aspects of cooperative social behavior and responding latency, i.e. impulsivity, in a variety of experimental models of anxiety and depression. The clinical efficacy of the so-called selective serotonin reuptake inhibitors (SSRIs) in disorders characterized by poor impulse control, e.g. bulimia nervosa, obsessive-compulsive disorder (OCD) and violent suicidal or homicidal behavior, may likewise be due to improved responding latency.

In 1968 Thoenen & Tranzer (1) discovered that the long-lasting depletion of NA in sympathetically innervated organs by 6-OH-DA is due to degeneration of NA terminals. This provided the basis for the development of a new concept in neurobiological research: the method of selective chemical neurodegeneration. The successful application of this method to produce degeneration of DA and NA neurons in brain (2,3) stimulated a search for compounds with comparable effects on central 5-HT neurons. In studies with a restricted number of 5-HT analogs, we were able to show that certain dihydroxylated tryptamines caused toxic damage to serotonin terminals. The recent findings by Björklund, Baumgarten & Rensch (4) and Gerson & Baldessarini (5) that DMI treatment prior to intraventricular 5,7-DHT injection prevents the damaging effect of the latter drug on NA but not on 5-HT neurons indicate that powerful and probably rather selective destruction of central indoleamine-containing axons and terminals can be achieved.

The authors describe the anatomical features and physiological properties of central serotonergic neurons. The central serotonin neurons (part of which store peptides [substance P, TRF, enkephalins] in addition to 5HT) are highly collateralized reticular-type brain stem neurons receiving multi-modal afferent information from ascending sensory and descending motor pathways. They are under control by noradrenergic, peptidergic and and gaba-ergic projection neurons and interneurons. Furthermore, they establish variable synaptoid and synaptic contacts to neuronal, glial and secretory targets throughout the entire neuraxis and send terminal branches into the ventricular CSF space. Firing rate and transmission activity appear to be controlled in a complex and rather rigid manner by 5HT release-dependent dendrodendritic and dendrosomatic inhibition via autoreceptors (which also regulate release at the axon terminals) and via transsynaptic inhibitory feedback circuits which may involve gabaergic projection and interneurons. 3H-imipramine appears to bind to an "imipramine recognition site" in the vicinity of the 5HT carrier, and to a variety of other transport and (postsynaptic) receptor sites (NA uptake, H1, 5HT2- and alpha 1-binding sites). Circumstantial evidence points to an as yet undetermined role of the postsynaptic 5HT-1-binding sites in neurotransmission. 5HT-2-binding sites fulfil the criteria for receptors: binding affinity of antagonists to these sites correlates significantly with their potency to inhibit behavioral excitation in rats elicited by 5-hydroxytryptophan or 5HT agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

In the isolated, perfused kidney of untreated and catcholamine-depleted rats (by 6-hydroxydopamine and reserpine), dopamine (DA) caused a dose-dependent increase in vascular resistance which could be prevented by prior blockade of the alpha-adreno-receptors. The DA-induced vasoconstriction thus appears to be due to a direct stimulation of alpha-receptors in the kidney rather than an indirect sympathomimetic effect through release of noradrena-line from local adrenergic nerve terminals. The effectiveness of the chemical sympathectomy accomplished with 6-hydroxydopamine and reserpine was evaluated by chemical; histochemical and electron microscopical methods.

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