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Abstract: The limbic system is composed of cortical as well as subcortical structures, which are intimately interconnected. The resulting macrostructure is responsible for the generation and expression of motivational and affective states. Especially high levels of serotonin are found in limbic forebrain structures. Serotonin projections to these structures, which arise from serotonergic cell body groups in the midbrain, form a dense plexus of axonal processes. In many areas of the limbic system, serotonergic neurotransmission can best be described as paracrine or volume transmission, and thus serotonin is believed to play a neuromodulatory role in the brain. Serotonergic projections to limbic structures, arising primarily from the dorsal and median raphe nuclei, compose two distinct serotonergic systems differing in their topographic organization, electrophysiological characteristics, morphology, as well as sensitivity to neurotoxins and perhaps psychoactive or therapeutic agents. These differences may be extremely important in understanding the role of these two serotonergic systems in normal brain function and in mental illness. Central serotonergic neurons or receptors are targets for a variety of therapeutic agents used in the treatment of disorders of the limbic system. [Copyright &y& Elsevier]

Cochlear serotonergic innervation is constituted by efferent fibers projecting both to the area below the inner and the outer hair cells. Previous detection of serotonin (5-HT) metabolites and 5-HT receptor mRNAs suggests the existence of serotonergic synaptic activity in the cochlea. The present study explores this possibility through the effect of 6-nitroquipazine (6-NQ), a 5-HT selective reuptake inhibitor, on the basal turnover of 5-HT. The concentrations of 5-HT and its metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) were quantified by high performance liquid chromatography with electrochemical detection in blood-free cochleae of rats treated with 6-NQ or saline and kept under silent conditions. Treatment with 6-NQ induced a significant increase of the cochlear concentration of 5-HT and a significant reduction of 5-HIAA concentration with respect to saline treatment. These findings could indicate that 6-NQ induced the blockade of the 5-HT selective reuptake to the cochlear serotonergic fibers. This suggests that plasma membrane 5-HT transporters are present in cochlear serotonergic fibers. Even though the role of serotonergic innervation on cochlear physiology remains unknown, the existence of cochlear serotonergic synaptic activity is strongly supported by present contributions. [Copyright &y& Elsevier]

Parkinson's disease (PD) is characterized by dopaminergic neurodegeneration in the substantia nigra and dopamine depletion in the striatum. Non-dopaminergic systems are also affected, including the serotonergic system. Enhanced striatal serotonergic innervation is a proposed compensatory mechanism for the dopaminergic deficit. Meanwhile a serotonergic deficit has been suggested as preceding the nigrostriatal dopaminergic pathology in PD. Our aim was to assess the serotonergic innervation of the striatum in a model of progressive experimental parkinsonism in macaques, from pre-symptomatic to symptomatic stages. The neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) was administered to adult macaque monkeys using a slow intoxication protocol. The intoxicated animals were classified into asymptomatic, recovered, moderate and severe parkinsonian, based on their motor behavior. The serotonergic innervation was studied by immunohistochemistry against serotonin (5-HT). In the striatum, the density of 5-HT-immunoreactive (5-HT+) axons was estimated with stereology. Images of the striatum in the immunostained sections were taken to compare the distribution patterns of the serotonergic innervation between groups. These patterns were apparently similar among the groups. Axonal density estimations showed no differences in striatal 5-HT+ innervation between the intoxicated groups and the control group. Accordingly, this study fails to find significant changes in the striatal serotonergic axonal innervation in MPTP-treated monkeys, coinciding with previous biochemical findings in our model. However, it is possible that alterations in the serotonergic system in PD could be independent of axonal density changes. Consequently, the proposed role for striatal serotonin serving as a compensatory mechanism for dopaminergic denervation merits further study. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'. • Enhanced and reduced striatal 5-HT innervation have been purported in parkinsonism. • The length density of serotonergic axons does not change in parkinsonian monkeys. • Serotonergic alterations, if present, may be independent of axonal density changes. [ABSTRACT FROM AUTHOR]