SEARCH · PubMed Health

Results for “Dihydroxytryptamines”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 613 records · Page 34Linked to original sources

PubMed1999

Serotonin depletion in the adult rat produces differential changes in highly polysialylated form of neural cell adhesion molecule and tenascin-C immunoreactivity.

Levels of immunoreactivity for highly polysialylated neural cell adhesion molecule (PSA-NCAM), NCAM, and tenascin-C (TN-C), were examined in the basal ganglia regions and hypothalamic nuclei of adult rats after serotonergic (5-HT) lesions induced by 5,7-dihydroxytryptamine injections in the dorsal and medial raphe nuclei. Decreases in the density of serotonin fibers were associated with no changes in NCAM and general decreases in PSA-NCAM staining, the time-course of changes being selective for each region. Taken that the confocal analysis indicated that serotonin neurons do not express PSA-NCAM and that similar decreases in PSA-NCAM staining were observed after inhibition of 5-HT synthesis induced by parachlorophenylalanine administration, these results suggest that 5-HT may reduce adhesion by acting on PSA-NCAM expression in its environment, and thus facilitate plasticity in adult brain. Two months after the neurotoxin lesions, a normalization of PSA-NCAM staining was associated with a partial restoration in 5-HT fiber density in the nucleus accumbens and the supraoptic nucleus, suggesting that PSA-NCAM may facilitate sprouting of 5-HT fibers. Since a similar normalization was also detected in the suprachiasmatic nucleus, which remained deprived of serotonin fibers, negative factors are likely to be involved in regeneration processes. Indeed, increases in glial fibrillary acidic protein (GFAP) followed by increases in TN-C were observed in these areas, suggesting that the secretion of TN-C by astrocytes may have negative consequences on the sprouting of 5-HT fibers. Finally, the lack of changes in striatal PSA-NCAM or TN-C staining observed after selective lesions of the dopaminergic pathway induced by intranigral injections of 6-hydroxydopamine indicates that 5-HT has a selective and critical role in adult brain plasticity.

5,7-Dihydroxytryptamine↗

PubMed1999

Developmental regulation of the serotonergic transmitter phenotype in rostral and caudal raphe neurons by transforming growth factor-betas.

Serotonergic (5-HT) neurons of the CNS develop as two separate clusters, a rostral and a caudal group, within the brain stem raphe. We show here that the transforming growth factors -beta2 and -beta3 (TGF-beta) and the TGF-beta type II receptor are expressed in the embryonic rat raphe, when 5-HT neurons develop and differentiate. To investigate putative roles of TGF-betas in the regulation of 5-HT neuron development we have generated serum-free cultures isolated either from the rostral or the caudal embryonic rat raphe, respectively. In cultures from the caudal E14 raphe saturating concentrations (5 ng/ml) of TGF-beta2 and -beta3 augmented numbers of tryptophan hydroxylase (TpOH) -immunoreactive neurons and cells specifically taking up 5,7-dihydroxytryptamine (5,7-DHT) by about 1.7-fold over a period of 4 days. Treatment with TGF-betas also increased uptake of 3H-5HT uptake about 1.7-fold. Alterations in 5-HT neuron numbers were due to the induction of serotonergic markers rather than increased survival, as shown by the efficacy of delayed short-term treatments. Comparing rostral and caudal raphe cultures from different embryonic ages suggests that distinct effects of TGF-betas reflect the responsiveness of 5-HT neurons at different ages rather than of different origins.

5,7-Dihydroxytryptamine↗

PubMed1996

Characterization of substance P release from the intermediate area of rat thoracic spinal cord.

Substance P (SP) nerve terminals innervate the intermediolateral cell column (IML) of the thoracic spinal cord, where SP coexists with serotonin (5-HT), neurokinin A (NKA) and thyrotropin-releasing hormone (TRH). Neither the depolarization-induced release of SP nor the presence of other neurochemicals in the regulation of SP release has been directly studied in this system. In the present study, basal and K(+)-stimulated release of SP from the microdissected intermediate area (including the IML, intercalated nucleus and central autonomic nucleus) of the rat thoracic spinal cord, and the regulation of SP release by presynaptic autoreceptors and by coexisting neurochemicals (5-HT, NKA and TRH) were studied using an in vitro superfusion system. Potassium evoked a concentration- and extracellular Ca(2+)-dependent release of SP. In rats pretreated with the serotoninergic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), both SP content and the absolute amount of SP released were decreased. However, the fraction of the remaining tissue content of SP released by K+ depolarization was not changed subsequent to 5,7-DHT treatment. Moreover, 5-HT, 5-HT1B agonists (CGS-12066B and RU 24969) and a 5-HT3 agonist (2-methyl-5-HT) did not alter the K(+)-evoked release of SP. These data demonstrate that SP is released from the intermediate area of the rat thoracic spinal cord and some of the SP released comes from serotoninergic nerve terminals. Although 5-HT coexists with SP in the IML, neither endogenous 5-HT nor 5-HT receptor ligands appear to regulate the release of SP. Other colocalized neuropeptides (NKA and TRH) are not involved in the regulation of SP release because neither NKA, a NK2 agonist (GR 64349) nor a TRH analog (MK-771) changed the K(+)-evoked release of SP. A neurokinin-1 (NK1) antagonist (GR 82334) dose-dependently (10(-9)-10(-7) M) increased the K(+)-stimulated release of SP. These data suggest the presence of presynaptic inhibitory NK1 autoreceptors. Whereas, NK1 agonists, [GR 73632 (10(-9)-10(-6) M) and [Sar9, Met (O2)11]SP (10(-8)-10(-6) M)], increased the basal and K(+)-stimulated release of SP, the excitatory effects of GR 73632 were not blocked by the NK1 antagonist. Moreover, GR 73632 increased the efflus of SP to a greater extent in the absence of peptidase inhibitors. Thus, the effect of NK1 agonists on the release of SP may be related to an inhibition of peptide degradation rather than activation of NK1 autoreceptors.

5,7-Dihydroxytryptamine↗

PubMed1998

Basal and stimulated extracellular serotonin concentration in the brain of rats with altered serotonin uptake.

We examined the relationship between the density of serotonergic (5-hydroxytryptamine [5-HT]) uptake sites and extracellular 5-HT concentration in the rat brain using microdialysis with two different models, lesions with 5,7-dihydroxytryptamine (50 microg in the dorsal raphe nucleus (DRN) 15 days before) and sublines of rats genetically selected displaying extreme values of platelet 5-HT uptake. Compared to controls, lesioned rats had a reduced cortical concentration of 5-hydroxyindoles (45%), unchanged basal extracellular 5-HT in the DRN and ventral hippocampus (VHPC), and reduced basal 5-hydroxyindoleacetic acid (5-HIAA) concentrations (46%, DRN; 22%, VHPC). Yet the perfusion of 100 mmol/L KCl or 1 micromol/L citalopram elevated dialysate 5-HT significantly more in the DRN and VHPC of controls. In genetically selected rats, platelet 5-HT content and uptake were highly correlated (r2 = 0.9145). Baseline dialysate 5-HT (VHPC) was not different between high and low 5-HT rats and from normal Wistar rats. However, KCl or citalopram perfusion increased dialysate 5-HT significantly more in high 5-HT than in low 5-HT rats, and the former displayed a greater in vivo tissue 5-HT recovery. Significant but small differences in the same direction were noted in [3H]citalopram binding in several brain areas, as measured autoradiographically. Thus, basal extracellular 5-HT (but not 5-HIAA) concentrations are largely independent on the density of serotonergic innervation and associated changes in uptake sites. However, marked differences emerge during axonal depolarization or reuptake blockade. The significance of these findings for the treatment of mood disorders in patients with neurological disorders is discussed.

5,7-Dihydroxytryptamine↗

PubMed1999

Origin of the serotonergic innervation to the rat dorsolateral hypothalamus: retrograde transport of cholera toxin and upregulation of tryptophan hydroxylase mRNA expression following selective nerve terminals lesion.

The regulation of serotonin synthesis was investigated in the serotonergic neurons, which provide afferents to the dorsolateral hypothalamus (DLH). The origin of the DLH projection neurons within the raphe nucleus was identified by retrograde transport of Cholera toxin (CTb) and their serotonergic nature confirmed by tryptophan hydroxylase (TPH) immunocytochemistry. Disruption of serotonin synthesis steady-state was induced unilaterally by a selective and local destruction of serotonergic nerve terminals with 5,7-dihydroxytryptamine (5,7-DHT), stereotaxically injected in the right DLH. The results show that most of the serotonergic dorsal raphe neurons projecting to the DLH have an ipsilateral localization within the lateral aspects of the nucleus. In rats with unilateral DLH lesion, a population of serotonergic cells within the raphe nucleus exhibited a clear increase in TPH mRNA. These cells were about five times more numerous in the ipsilateral as compared to the contralateral dorsal raphe nucleus and they had, for the most part, a lateral localization within the raphe nucleus. Sham-operated rats did not exhibit any upregulation of TPH mRNA. Together, the present results provide the first demonstration that a discreet and selective destruction of serotonergic terminals induces a circumscribed and striking increase in TPH mRNA expression in a subset of brainstem serotonergic neurons projecting to and/or passing through the DLH. On the basis of these results and previous in vivo measurements of TPH activity (e.g., 5-HT synthesis), we suggest that this upregulation in TPH mRNA expression results from the loss of pre-synaptic and/or post-synaptic regulation of serotonin synthesis. These new findings raise important issues related to the repercussions of a local disruption in serotonergic neurotransmission on brain areas remote from the site of injury.

5,7-Dihydroxytryptamine↗

PubMed2000

Fenfluramine-induced increase in preproenkephalin mRNA levels in the striatum: interaction between the serotonergic, glutamatergic, and dopaminergic systems.

Fenfluramine (FE) is a halogenated amphetamine derivative that has been used in the treatment of obesity. It has been suggested that the effects of FE on the striatum are mediated by serotonergic mechanisms. However, several major afferent systems may be involved, and administration of FE may be useful to study interactions between these systems. In this work, the effects of FE on striatopallidal neurons and the possible involvement of the major striatal afferent systems were studied in rats by determination of FE-induced changes in striatal levels of preproenkephalin (PPE) mRNA using in situ hybridization. Injection of FE induced a significant increase (60%) in striatal levels of PPE mRNA. This increase was blocked by pretreatment with the D(1) dopamine receptor antagonist SCH-23390 or with the NMDA glutamate receptor antagonist MK-801, or by lesion of the serotonergic system with 5,7-dihydroxytryptamine or p-chlorophenylalanine. In 6-hydroxydopamine lesioned rats, the lesion-induced increase in PPE mRNA levels was not affected by injection of FE, but was reduced by simultaneous serotonergic deafferentation. The results suggest that the serotonergic, glutamatergic, and dopaminergic system interact to increase striatal PPE mRNA levels after FE administration.

5,7-Dihydroxytryptamine↗

PubMed2000

Dorsal raphe stimulation differentially modulates dopaminergic neurons in the ventral tegmental area and substantia nigra.

The serotoninergic (5-HT) input from the dorsal raphe nucleus (DRN) to midbrain dopamine (DA) neurons is one of the most prominent. In this study, using standard extracellular single cell recording techniques we investigated the effects of electrical stimulation of the DRN on the spontaneous activity of substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA) DA neurons in anesthetized rats. Poststimulus time histograms (PSTH) revealed two different types of response in both SNpc and VTA. Some cells exhibited an inhibition-excitation response while in other DA neurons the initial response was an excitation followed by an inhibition. In SNpc, 56% of the DA cells recorded were initially inhibited and 31% of the DA cells were initially excited. In contrast, 63% of VTA DA cells were initially excited and 34% were initially inhibited. Depletion of endogenous 5-HT by the neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), and the 5-HT synthesis inhibitor para-chlorophenylalanine (PCPA), almost completely eliminated the inhibition-excitation response in both SNpc and VTA DA cells, without changing the percentage of DA cells initially excited. Consequently, the proportion of DA neurons that were not affected by DR stimulation increased after 5-HT depletion (from 13% to 60% in SNpc and from 6% to 31% in VTA). In several DA cells, DRN stimulation caused important changes in firing rate and firing pattern. These data strongly suggest that the 5-HT input from the DRN is mainly inhibitory. It also suggests that 5-HT afferences modulate SNpc and VTA DA neurons in an opposite manner. Our results also suggest that non-5-HT inputs from DR can also modulate mesencephalic DA neurons. A differential modulation of VTA and SNpc DA neurons by 5-HT afferences from the DRN could have important implications for the development of drugs to treat schizophrenia or other neurologic and psychiatric diseases in which DA neurons are involved.

5,7-Dihydroxytryptamine↗

PubMed2000

Brain-derived neurotrophic factor and trkB are essential for cAMP-mediated induction of the serotonergic neuronal phenotype.

Serotonergic neurons in the central nervous system are crucial in the control of autonomic functions and behavior. Mechanisms by which development and maintenance of the serotonergic transmitter phenotype is regulated include activation of protein kinase A (PKA). Using cultures established from the E14 rat raphe we show here that forskolin (10 microM) increases numbers of neurons expressing tryptophan hydroxylase (TpOH), the key enzyme of serotonin synthesis, and uptake of the false serotonergic transmitter 5, 7-dihydroxytryptamine (5,7-DHT). As shown by short-term treatments the effect is due to phenotype induction rather than survival. To begin to understand downstream or parallel signaling pathways required for the PKA-mediated induction of serotonergic markers, we have studied the putative implication of brain-derived neurotrophic factor (BDNF) and its receptor trkB. Treatment of raphe neurons with forskolin induced BDNF mRNA assayed by competitive RT-PCR. Moreover, trkB-IgG receptor bodies fully prevented the forskolin-induced numerical increase in TpOH- and 5,7-DHT-positive cells suggesting an implication of a TrkB-activated pathway. TrkC-IgG had no effect. K252b, a specific inhibitor of trk kinase activity likewise abolished the induction of serotonergic markers by forskolin. In turn, the inductive effect of BDNF on serotonergic markers was blocked by KT5720, a specific inhibitor of PKA. Taken together, these data suggest that co-activation of cAMP- and trkB-dependent signaling pathways plays a crucial role in the regulation of the serotonergic neuronal phenotype.

5,7-Dihydroxytryptamine↗

PubMed2001

Effects of serotonin depletion on local interneurons in the developing olfactory pathway of lobsters.

During embryonic life, the growth of the olfactory and accessory lobes of the lobster brain is retarded by serotonin depletion using 5,7-dihydroxytryptamine (5,7-DHT) (Benton et al., 1997). The local and projection interneurons that synapse with chemosensory cells in the olfactory lobes are potential targets of this depletion. This study documents proliferation and survival in the local interneuron cell clusters, and examines the differentiation of a prominent local interneuron, the serotonergic dorsal giant neuron (DGN), following serotonin depletion. An increase in dye coupling between the DGN and nearby cells is seen after serotonin depletion. However, morphometric analyses of individual DGNs in normal, sham-injected, and 5,7-DHT-treated embryos show that the general morphology and size of the DGNs are not significantly altered by serotonin depletion. Thus, the DGN axonal arbor occupies a greater proportion of the reduced olfactory lobes in the 5,7-DHT-treated embryos than in normal and sham-injected groups. The paired olfactory globular tract neutrophils (OGTNs), where olfactory interneurons synapse onto the DGNs, are 75% smaller in volume than the comparable region in either sham-injected or normal embryos. In vivo experiments using bromodeoxyuridine (BrdU) show that proliferation in the local interneuron soma clusters is reduced by 5,7-DHT treatment and that survival of newly proliferated local interneurons is also compromised. Our data suggest that alterations in the growth of the DGNs do not contribute to the dramatic reduction in size of the olfactory neutrophils following serotonin depletion, but that cell proliferation and survival among the local interneurons are regulated by serotonin during development. Reduced numbers of local interneurons are therefore one likely reason for the growth reduction observed after serotonin depletion.

5,7-Dihydroxytryptamine↗

PubMed1982

Substance P in nociceptive sensory neurons.

Substance P is contained within a subpopulation of nociceptive primary sensory neurons that project to the superficial dorsal horn of the spinal cord. Stimulation of the peripheral processes of primary afferent fibres at intensities that activate A delta and C fibres elicits a pronounced release of substance P from the cat spinal cord in vivo. Experiments with the neurotoxins capsaicin and 5,6-dihydroxytryptamine have shown that substance P release from the spinal cord in vivo derives largely from afferent fibres. Intrathecal perfusion of the cat spinal cord with morphine abolishes the nerve-evoked release of substance P while capsaicin produces a dramatic increase in peptide release. Prolonged treatment of rats with capsaicin depletes substance P from the dorsal horn and results in reduced sensitivity to noxious peripheral stimuli. The duration of the somatic action potential recorded from cultured sensory neurons is known to be decreased by enkephalin and is prolonged by capsaicin. The acute effects of both morphine and capsaicin on substance P may be mediated by an interaction with voltage-sensitive ion channels on the sensory neuron. These observations suggest that nociceptive input to the dorsal horn can be regulated by drugs that interact directly with substance P-containing sensory terminals.

5,6-Dihydroxytryptamine↗

PubMed2001

Neonatally elevated serotonin levels alter terminal arbors of individual retinal ganglion cells in superior colliculus of hamsters.

Previous studies from this laboratory showed that sprouting of serotoninergic (5-HT) axons in the hamster's superior colliculus (SC), induced by a single subcutaneous injection of 5,7-dihydroxytryptamine (5,7-DHT) at birth (postnatal day 0 [P-0]), resulted in an increased terminal distribution of the uncrossed retinocollicular projection that was not associated with any changes in the number or distribution of ipsilaterally projecting retinal ganglion cells. The present study was undertaken to determine what effect this manipulation had on the terminal arbors of such axons. Retinocollicular axons of normal and 5,7-DHT-treated animals were anterogradely labeled with small intraretinal injections of the lipophilic dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) on P-16. After tissue processing on P-19, single retinocollicular axon arbors were reconstructed by using confocal microscopy. Quantitative analysis indicated that arbors from 5,7-DHT-treated hamsters had significantly greater total fiber lengths, areas, and volumes than those from normal animals. There were no differences between axons from the two groups in number of branch points, distribution of relative branch lengths, and numbers of bouton-like swellings. These results support the hypothesis that increased SC concentrations of 5-HT alter development of the uncrossed retinocollicular pathway such that a greater territory is covered by individual terminal arbors but that the number of synaptic contacts per arbor remains constant. This may explain, at least in part, the abnormally widespread distribution of the aggregate ipsilateral projection.

5,7-Dihydroxytryptamine↗

PubMed1975

Hippocampal innervation by serotonin neurons of the midbrain raphe in the rat.

The organization of the brainstem serotonin neuron projection to the hippocampal formation was analyzed in the rat. This projection arises in the raphe nuclei of the midbrain. Following destruction of the midbrain raphe nuclei, chiefly nucleus centralis superior, there is a 72% decrease in hippocampal serotonin content. Injection of tritiated amino acid into the midbrain raphe nuclei results in transport of tritiated protein to the hippocampal formation and this transport is blocked in animals pretreated by intraventricular administration of 5,6-dihydroxytryptamine (5,6-DHT). Autoradiographic analysis indicates that the transport reaches the hippocampal formation primarily via two major pathways, the cingulum and the fornix. Cingulum fibers terminate predominantly in the dorsal hippocampus whereas the fornix distributes throughout the entire hippocampal formation. Some fibers reach the ventral hippocampus from the entorhinal area. Within the hippocampus there is dense labeling in a restricted lamina of the CA1 stratum lacunosum-moleculare with moderate labeling in stratum radiatum. Stratum oriens is sparsely labeled in CA1 and moderately so in CA2 and CA3. Stratum radiatum and stratum lacunosum-moleculare are moderately densely labeled in CA2 and Ca3. The area dentata is sparsely to moderately labeled in the molecular layer and heavily labeled in a thin lamina of the hilar zone immediately beneath the granule cell layer. The remaining hilar zone is moderately labeled. All of the discrete labeling of the hippocampus and area dentata described above is absent in animals pretreated with 5,6-DHT. These observations indicate that serotonin neurons of the midbrain raphe provide a highly organized innervation of the hippocampal formation in the rat.

5,6-Dihydroxytryptamine↗

PubMed1982

Identification of and interactions between noradrenergic and serotonergic neurites in the myenteric plexus.

Interactions between enteric noradrenergic and serotonergic neurites in the myenteric plexus were examined. The influence of exogenous norepinephrine (NE) and endogenously released NE on the release of 3H-serotonin (3H-5-HT) from electrically stimulated, everted segments of guinea pig small intestine were analyzed. In addition, methods were employed to permit the ultrastructural identification of enteric serotonergic and noradrenergic neurites. These included electron microscopic radioautographic localization of 3H-5-HT in gut from animals treated with 6-hydroxydopamine (6-HD; 100 mg/kg) and examination of NaMnO4-fixed tissue from animals given desmethylimipramine and the indolic neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT). Exogenous NE antagonized the stimulated release of 3H-5-HT; this action was mediated through alpha adrenoceptors. Evidence was obtained, however, that endogenous NE liberated from sympathetic postganglionic nerve terminals had a different action on the stimulated release of 3H-5-HT from that of exogenous NE. Endogenous NE appeared to facilitate 3H-5-HT release through an action on beta adrenoceptors. Terminals identified as probably serotonergic by radioautographic labeling with 3H-5-HT or by loading with 5,7-DHT were most often found to end on neuronal somata or proximal dendrites. Synaptic specializations were found by radioautography in these locations. Terminals, dendrites, and cell bodies that took up 5,7-DHT could be identified in NaMnO4-fixed material that also permitted the simultaneous recognition of noradrenergic varicosities. Apparent noradrenergic-serotonergic axoaxonic contacts were found by means of this double-labeling technique. Together with the results of the experiments on the release of 3H-5-HT, these anatomical observations suggest that noradrenergic axons form facilitatory axoaxonic synapses with enteric serotonergic neurons.

5,7-Dihydroxytryptamine↗

PubMed1982

Electron microscopical observations on the indoleamine-accumulating neurons and their synaptic connections in the retina of the cat.

The distribution of indoleamine-accumulating amacrine cells and their synaptic connections in the retina of the cat were analyzed in the fluorescence, phase-contrast, and electron microscopes. The findings were compared to recently characterized morphological subclasses of amacrine cells. The indoleamine-accumulating neurons were visualized after labeling with an exogenous indoleamine, 5,6-dihydroxytryptamine. The intravitreal injection of the labeling drug was preceded by treatment with the neurotoxic dopamine-analogue, 6-hydroxydopamine, in order to destroy the otherwise interfering dopaminergic processes. The analysis in the fluorescence and phase-contrast microscopes confirmed earlier reports that the indoleamine-accumulating cell bodies and processes have a redistribution consistent with that of amacrine cells. A stratified branching pattern of the indoleamine-accumulating processes in the outer half of the inner plexiform layer was discovered. In the inner half of that layer the branching pattern is diffuse. In the electron microscope the indoleamine-accumulating neurons were seen to have synapses fo the conventional type. Their main synaptic contacts are reciprocal synapses with rod bipolar terminals in sublamina b of the inner plexiform layer. They also have synapses with flat cone bipolar terminals in sublamina a, and occasionally with amacrine cells and ganglion cells throughout the inner plexiform layer. Synapses with invaginating cone bipolar terminals, in sublamina b, appear to be rare. The synaptic arrangement with reciprocal synapses with rod bipolar terminals is similar to that of the recently reported AI amacrine cells. It is also similar to that of the indoleamine-accumulating neurons in the retinae of other mammals investigated earlier.

5,6-Dihydroxytryptamine↗

PubMed1984

Embryonic development of monoaminergic neurons in the chick retina.

By means of a histofluorescence technique, embryonic and postnatal development of monoaminergic neurons was followed in the chicken retina with or without intravitreal injection of monoamines 30-60 minutes before eye removal. Fluorescent cells were tentatively classified into five subsets with respect to the soma shape, localization, migration of somata during retinal development, uptake capacity (color and intensity in fluorescence), and sensitivity to neurotoxins. The five subsets of cells were endogenous dopaminergic (DA), catecholamine-accumulating (CA), indoleamine-accumulating (IA), CA-bipolarlike, and IA-bipolarlike cells. Greenish endogenous DA-cells first appeared at the 14-15th embryonic day. The cell body of DA-cells was initially fusiform and located slightly distal to the innermost level of the inner nuclear layer (INL). They became round or oval and migrated to the innermost level of the INL by day 20. Both large and small bottle-shaped CA-cells were visualized at an intermediate portion of INL by intravitreal injection of exogenously applied dopamine or noradrenaline (1-2 micrograms/eye) at day 10. Large bottle-shaped cells, like the DA cells, changed to round or oval and migrated to the innermost level of the INL by day 20. On the other hand, small bottle-shaped CA-cells retained their cell shape and location in the INL as retinal development progressed. Therefore, the large bottle-shaped CA-cells seen in an early developmental stage correspond to the DA-cells. IA-cells were visualized one or two cell rows outward in the INL first at day 13-14 by intravitreal injection of 5,6-dihydroxytryptamine or 5-hydroxytryptamine (1-5 micrograms).(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine↗

PubMed1989

Serotoninergic neurons in the retina of Xenopus laevis: selective staining, identification, development, and content.

Uptake of 3H-serotonin followed by autoradiography, and uptake of the serotonin analog 5,7-dihydroxytryptamine (5,7-DHT), with subsequent staining, were each used to define a unique set of neurons in the retina of the African clawed frog, Xenopus laevis. Both techniques demonstrated the same population of neurons, on the basis of perikaryal size, shape, and position within the retina. Two classes of amacrine cells accumulated 5,7-DHT at the proximal (vitread) margin of the inner nuclear layer; the two classes were distinguished by the size of their perikarya. Two similar populations of cells, observed in the ganglion cell layer with lower frequency, may represent "displaced" counterparts of these two amacrine cell types. A class of bipolar cells whose perikarya were located in middle-to-distal regions of the inner nuclear layer also accumulated 5,7-DHT and 3H-serotonin. Processes of these cells contributed to a dense plexus of fine fibers that appeared evenly distributed throughout the inner plexiform layer. 3H-Serotonin-accumulating cells first appeared in the developing retina at stage 35/36, a time immediately after retinal stratification but before elaboration of either plexiform layer. Electron microscopic analysis permitted an identification of 3H-serotonin-accumulating terminals in the inner plexiform layer. Serotonin-labeled terminals containing conventional contacts, suggestive of amacrine cells, were presynaptic to unidentified processes and postsynaptic to bipolar cells. Labeled terminals containing ribbon contacts, indicative of bipolar cells, were postsynaptic to amacrine cells. The amount of serotonin contained in isolated retinas was 15 pmol/mg protein as measured by HPLC with electrochemical detection. We attempted to stimulate the release of accumulated 3H-serotonin from mature retinas by increasing the K+-concentration in the bathing medium. Although preloaded glycine is readily released from 14C-glycine-accumulating neurons, from the same retinas there was no calcium-dependent, K+-stimulated release of 3H-serotonin. This finding suggests that serotonin and glycine are processed differently by retinal neurons, the consequence of which results in differing responses to 40 mM K+.

5,7-Dihydroxytryptamine↗

PubMed1992

All indoleamine-accumulating cells in the rabbit retina contain GABA.

The indoleamine-accumulating amacrine cells of the rabbit retina are wide-field and numerous. They form a dense plexus in sublamina 5 of the inner plexiform layer where they make reciprocal synapses with rod bipolar cells. To provide a quantitative test for the colocalization of serotonin (5-HT) and gamma-aminobutyric acid (GABA) in the rabbit retina, we designed two parallel double-label experiments. In the first series, the indoleamine-accumulating cells were labeled with 5,7-dihydroxytryptamine (5,7-DHT), which was subsequently visualized by photooxidation in the presence of diaminobenzidine. This was combined with autoradiography for 3H-muscimol. In the second and complementary series, 3H-5-HT uptake was combined with postembedding GABA immunocytochemistry. These two experiments provided essentially identical results: over 98% of the indoleamine-accumulating amacrine cells were double-labeled. This means that, within the limit of experimental error, all the indoleamine-accumulating amacrine cells are GABAergic. The indoleamine-accumulating amacrine cells account for 15-20% of a large diverse group of GABA amacrine cells. In addition, the rare type 3 indoleamine-accumulating cells and fine processes running in the optic fiber layer were double-labeled. If there is insufficient 5-HT to support a transmitter role in the rabbit retina, our results suggest that the indoleamine-accumulating cells may use GABA as a neurotransmitter. Thus, rod bipolar cells, in common with other bipolar cell types, receive extensive negative feedback at GABA-mediated reciprocal synapses.

5,7-Dihydroxytryptamine↗

PubMed1993

Increased serotoninergic innervation of the hamster's superior colliculus alters retinotectal projections.

Anterograde tracing with horseradish peroxidase (HRP) was used to compare the organization of retinotectal projections in normal adult hamsters and in animals that sustained subcutaneous injections of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) on the day of birth. Neonatal injection of this neurotoxin decreases the density of the serotoninergic (5-HT) innervation of the cerebral and cerebellar cortices, but increases the density of these fibers in the brainstem including the superior colliculus (SC). Analysis of tissue from the retinorecipient laminae of the SC by high-pressure liquid chromatography indicated that these lesions increased the amount of 5-HT in the adult SC by 47%. The increased serotoninergic innervation of SC was associated with a marked change in the distribution of the uncrossed retinotectal projection. In normal adult hamsters, fibers from the ipsilateral eye form dense clusters in the lowermost stratum griseum superficiale (SGS) and stratum opticum (SO). A small number of uncrossed fibers are also visible in the more caudal portions of these layers. In the animals that sustained neonatal 5,7-DHT injections, uncrossed retinotectal fibers formed a nearly continuous band in rostral SO and lower SGS, and numerous labeled fibers were present in the caudal SC, primarily in the SO. Neonatal treatment with 5,7-DHT also produced alterations in the crossed retinotectal pathway and in the crossed and uncrossed retinogeniculate projections. These results indicate that the 5-HT input to the developing brainstem may strongly influence the development of retinofugal projections.

5,7-Dihydroxytryptamine↗