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 811 records · Page 45Linked to original sources

PubMed1992

Autoradiographic characterization of [3H]imipramine and [3H]citalopram binding in rat and human brain: species differences and relationships to serotonin innervation patterns.

The neuroanatomical distribution of binding sites for [3H]imipramine and [3H]citalopram was assessed by in vitro autoradiography in select regions of the rat and human forebrain. To determine involvement of serotonin-containing terminals in the binding of [3H]imipramine and [3H]citalopram, binding of these compounds was measured in rats after destroying serotonin-containing neurons with 5,7-dihydroxytryptamine (5,7-DHT). Treatment with this neurotoxin decreased serotonin content by 90% and reduced [3H]citalopram binding to a similar extent. These results demonstrate that [3H]citalopram binding is a reliable marker for serotonin-containing terminals. Binding of [3H]imipramine was reduced by only 15-35% after 5,7-DHT treatment. These latter results suggest that only a small fraction of [3H]imipramine binding to brain sections is associated with serotonergic terminals under standard conditions used in autoradiographic studies with the ligand. Dose-response effects of fluoxetine and desipramine on displacement of [3H]imipramine binding in forebrain regions indicate that the ligand labels predominantly high capacity, low affinity binding sites. To determine the utility of the rat brain as a model for [3H]imipramine and [3H]citalopram binding in the human brain, binding of the ligands was compared in human and rat hypothalamus, amygdala, and hippocampus. The pharmacological characteristics of [3H]imipramine and [3H]citalopram binding were similar in the rat and human brain. However, substantial species differences were observed in topographic patterns of [3H]imipramine binding within the hippocampus and hypothalamus. The distribution of [3H]citalopram binding sites within the amygdala and hypothalamus were also strikingly different in rats compared to humans. This work provides the first demonstration that marked species differences exist in the topography of serotonergic innervation and in the distribution of [3H]imipramine binding sites within the rat and human brain regions examined.

5,7-Dihydroxytryptamine↗

PubMed1993

Separate neural pathways respond to different noxious stimuli affecting respiratory pump frequency in Aplysia fasciata.

Neural circuits responsible for both conditioned and unconditioned respiratory pumping to three stimuli modulating respiratory pumping were examined. The stimuli used were: (i) reduction of pH; (ii) increase and (iii) decrease in seawater concentration. Ablation of the osphradium, but not of the rhinophores, abolished responses to all 3 stimuli. Cutting the pleural-abdominal connectives led to a decrease in responses to lowered pH, but did not affect responses to changes in seawater concentration. Further lesions showed that integrity of the cerebral-pleural ganglion is needed for animals to respond to a decrease in pH. Thus, neural circuitry entirely within the abdominal ganglion and the periphery innervated by the ganglion is sufficient for mediating responses to changes in seawater concentration, while the cerebral ganglion is needed to respond to lowered pH. Different transmitter mechanisms are also used by pathways responding to changes in seawater concentration and to decreased pH: 5,7-dihydroxytryptamine in concentrations which cause depletion of serotonin blocked the response to lowered pH, but not to altered seawater concentrations.

5,7-Dihydroxytryptamine↗

PubMed1993

Involvement of noradrenergic and 5-hydroxytryptaminergic systems in allylnitrile-induced head twitching.

Allylnitrile induces in rats persistent behavioral abnormalities, including head twitching, following a single administration. We studied the role of 5-hydroxytryptamine (5-HT) and noradrenaline (NA) systems in the brain of rats in inducing and maintaining the head twitching. Allynitrile (1.49 mmol/kg) induced 5-HT system activation in all areas of the brain studied 1-4 days after oral administration, and a reduction in the content of NA in the hippocampus, cortex and hypothalamus 1 day after dosing, in the hippocampus, cortex, hypothalamus and midbrain 2 days after dosing, and in the hypothalamus 4 days after dosing. Allylnitrile induced no change in the content of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) or NA 7-28 days after dosing. Pretreatment with 5,7-dihydroxytryptamine (5,7-DHT) suppressed the allylnitrile-induced head twitching, and decreased the contents of 5-HT and 5-HIAA in almost all areas of the brain throughout the observation period, as well as the ratio of 5-HIAA/5-HT in the medulla oblongata plus pons from 1 to 30 days after dosing with allylnitrile. No change in NA was observed in any areas of the brain. Pretreatment with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) increased the head twitching induced by allylnitrile, and decreased the content of NA in all areas of the brain throughout the observation period, without any change in the contents of 5-HT or 5-HIAA or in the ratio of 5-HIAA/5-HT. The present results suggest the involvement of 5-HT and NA systems in allylnitrile-induced head twitching.

5,7-Dihydroxytryptamine↗

PubMed1993

Alterations of serotonin receptor binding in the hypothalamus following acute denervation.

Quantitative autoradiography was used to determine the effect of acute serotonergic denervation with 5,7-dihydroxytryptamine (5,7-DHT) or serotonin 5HT1a and 5-HT1b receptors in male rats. Seven days after intrahypothalamic 5,7-DHT injection there was a significant increase in the density of 5HT1a receptors in the ventromedial and dorsomedial hypothalamic nuclei (VMN and DMN) of male rats. In adjacent sections. 5-HT1b receptors were significantly increased only in the VMN. No changes in receptor density were observed in the lateral hypothalamic area or hippocampus even though binding of [3H]paroxetine, which labels the presynaptic transporter site, was significantly decreased in all evaluated brain regions in 5,7-DHT-treated animals. In addition to demonstrating that 5-HT1a and 5-HT1b receptors are differentially regulated in different brain areas, these results show that in the brain regions examined both 5-HT1a and 5-HT1b receptors are primarily post-synaptic.

5,7-Dihydroxytryptamine↗

PubMed1994

Impairment of serotoninergic transmission is followed by adaptive changes in 5HT1B binding sites in the rat suprachiasmatic nucleus.

Serotonin1B (5-HT1B) receptor binding in the suprachiasmatic nucleus (SCN) following impairment of serotoninergic transmission was studied by quantitative autoradiography. Serotonin (5-HT) denervation with 5,7-dihydroxytryptamine (5,7-DHT) caused a significant increase in the density of 5-HT1B receptors in both the ventral (62%) and dorsal (53%) parts of the SCN as early as 3 days after axotomy. The magnitude of this increase did not differ 3, 15 or 21 days post-lesion. An up-regulation of 5-HT1B receptors with similar magnitude was obtained in the two parts of the SCN after inhibition of 5-HT synthesis by chronic parachlorophenylalanine treatment. In this case, up-regulation was shown to be reversible after restoration of 5-HT synthesis with L-5-hydroxytryptophan. These results indicate that 5-HT1B receptor density in the SCN was inversely correlated with 5-HT levels. These plastic properties exhibited by 5-HT1B receptors in the SCN are discussed in relation to the mode of 5-HT transmission and possible localization of the receptors onto the main chemically defined cell populations of the nucleus.

5,7-Dihydroxytryptamine↗

PubMed1994

Autoradiographic characterization of binding sites for [3H]milnacipran, a new antidepressant drug, and their relationship to the serotonin transporter in rat brain.

Milnacipran is a new antidepressant drug and an equipotent inhibitor of the uptake of serotonin and noradrenaline. Quantitative autoradiography and radioligand binding studies were used to characterize recognition sites of [3H]milnacipran in rat brain. [3H]Milnacipran demonstrated saturable, reversible and nanomolar affinity binding. The binding was Na(+)-dependent, potently displaced by serotonin uptake inhibitors in all structures and moderately or weakly displaced by catecholamine uptake inhibitors (order of potency: paroxetine > fluoxetine > mazindol > desipramine > nomifensine > maprotiline). High density of recognition sites were found in structures dense in serotonergic innervation (raphe, basal ganglia, colliculi, cortex). The autoradiographic pattern of [3H]milnacipran recognition sites resembled that of [3H]paroxetine, but their distribution did not correlate well in some structures. Selective lesioning of serotonergic neurons by intracerebral injection of 5,7-dihydroxytryptamine caused a large decrease of [3H]milnacipran binding in various regions (septum, caudate, hippocampus, thalamus, ventral and dorsal hypothalamus), but in other structures, the [3H]milnacipran binding was partially affected (putamen) or even unchanged (amygdala, lateral hypothalamus). In contrast, lesion of noradrenergic neurons by intraperitoneal administration of [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine] did not affect the binding of [3H]milnacipran in any region. These results show that [3H]milnacipran mainly binds to the serotonin transporter and does not recognize the catecholamine transporters under the conditions used. In addition, [3H]milnacipran might also bind to other sites, serotonin transporter localized on non-serotonergic neurons or serotonergic neurons insensitive to 5,7-DHT neurotoxicity.

5,7-Dihydroxytryptamine↗

PubMed1994

An in vivo study of the effect of 5-HT and sympathetic nerves on transferrin and transthyretin mRNA expression in rat choroid plexus and meninges.

Brain expression of transferrin (Tf) and transthyretin (TTR) mRNA has been demonstrated in different species, TTR being found only in the choroid plexus. We report here that both these mRNAs are also expressed in the meninges. In vitro studies have shown that Tf secretion by the rat choroid plexus is stimulated by 5-hydroxytryptamine (5-HT) while sympathetic nerves regulate different transport functions in the same tissue. We have used various in vivo models to study the neuroendocrine regulation of Tf and TTR mRNA expression in the choroid plexus and meninges. Destruction of the serotonergic nerves in the brain by either raphe nuclei lesion or intraventricular injections of 5,7-dihydroxytryptamine (5,7-DHT), which both decreased brain 5-HT levels significantly, did not affect Tf or TTR mRNA levels in choroid plexus and meninges, but increased TTR mRNA in liver. Intraventricular injection of 10 or 100 pmol 5-HT did not change the expression of these proteins in any of the tissues studied. Removal of the sympathetic innervation to the choroid plexus by cervical sympathectomy did not affect Tf or TTR mRNA levels in choroid plexus and liver, nor the incorporation of radioactive leucine into protein in various parts of the brain. In conclusion, our results do not support a regulatory role in vivo for neuronally derived 5-HT or sympathetic nerve activity on Tf and TTR mRNA expression in rat choroid plexus and meninges.

5,7-Dihydroxytryptamine↗

PubMed1994

Long-term astroglial reaction to serotonergic fiber degeneration.

Glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) expression were analysed by Western and Northern blotting in the hippocampus, the frontal and occipital cortex, and the cerebellum of the adult rat, as a manifestation of the astroglial reaction, 2 and 3 months after 5,7-dihydroxytryptamine injection into the lateral ventricule. 5HT injury stimulated GFAP and GS expression in a temporally and regionally specific fashion. At 2 months postlesion, the GFAP-mRNA and GFAP levels appeared enhanced but returned to control levels at 3 months. The GFAP-mRNA and GS-mRNA levels increased in the frontal cortex at 3 months. Such a delayed astroglial reactivity might implicate astrocytes in neurodegenerative disorders.

5,7-Dihydroxytryptamine↗

PubMed1996

Ipsilateral alterations in tryptophan hydroxylase activity in rat brain after hypothalamic 5,7-di-hydroxytryptamine lesion.

The in vivo relationship between the amounts of tryptophan hydroxylase (TPH) protein and its intrinsic synthetic activity, measured by quantifying the amounts of alpha-[3H]methyl-5-hydroxytryptamine (alpha-[3H]M5-HT), is reported in cell body and terminal areas of intact and disturbed serotonergic neurons following a unilateral 5,7-dihydroxytryptamine (5,7-DHT) lesion of the dorsolateral hypothalamus. Five days after the lesion, the relationships between TPH and its synthetic product 5-HT were evaluated on adjacent brain sections in serotonergic cells bodies of the dorsal raphe nucleus (DRN) and nerve fibres of the medial forebrain bundle (MFB). On the side contralateral to the lesion, TPH and alpha-[3H]M5-HT levels in the intact hemi-DRN exhibited a caudo-rostral distribution and were positively and significantly correlated (p < or = 0.001); the calculated TPH-specific activity was 0.76 nCi of alpha-[3H]M5-HT formed per U TPH. In the MFB, quantitative measurements of TPH and alpha-[3H]M5-HT showed no correlation between enzyme and product and no specific activity for TPH could be determined. On the side ipsilateral to the lesion, the density of TPH-immunoreactive fibers was drastically decreased in the dorsolateral hypothalamus where a significant reduction in TPH content (45.5% of control side, P < 0.001) was found. In the overall ipsilateral hemi-DRN, TPH and alpha-[3H]M5-HT levels, their correlation as well as TPH-specific activity were unaltered by the lesion but a significant increase in alpha-[3H]M5-HT and TPH contents was observed in the lateral wings of the DRN. The lesion also induced a significant increase in alpha-[3H]M5-HT and TPH levels (136% and 93.8%, P < 0.001, respectively) in the ipsilateral MFB, which resulted in a positive and significant correlation between these two markers and yielded a TPH-specific activity of 1.0 nCi of alpha-[3H]M5-HT formed per U TPH. TPH topological area was also significantly increased in the lateral aspect of the ipsilateral MFB 5 days post lesion. These results show that 5-HT synthesis in the intact DRN is proportional to and dependent on TPH activity while in the MFB, 5-HT accumulation appears unrelated to TPH content which is most likely in an inactive enzymatic form. Moreover, the data show that a local disruption of serotonergic terminals in the dorsolateral hypothalamus does not affect 5-HT synthesis in the overall ipsilateral DRN neurons but results in local activation of TPH within the serotonergic projection neurons and the ipsilateral MFB, as evidenced by active de novo synthesis of 5-HT. Altogether the results point to circumscribed activation of compensatory mechanisms in 5-HT synthesis after selective destruction of serotonergic terminals.

5,7-Dihydroxytryptamine↗

PubMed1996

Preprotachykinin and preproenkephalin mRNA expression within striatal subregions in response to altered serotonin transmission.

The effects of lowered serotonin (5-hydroxytryptamine; 5-HT) neurotransmission on preprotachykinin (PPT) and preproenkephalin (PPE) mRNA levels were examined in subregions of the striatum. Adult male rats were treated systemically with para-chlorophenylalanine (pCPA; 350 mg/kg single i.p. injection) which reduced forebrain 5-HT amounts to approximately 20% of saline-injected controls at 24 and 48 h. As measured by Northern analysis, PPT and PPE mRNA levels were elevated 50% and 160% respectively in the anterior ventromedial striatum (region included nucleus accumbens). PPT mRNA levels were raised 90% in posterior striatum (at the level of the globus pallidus) by 48 h post-pCPA injection. To determine if increased PPT and PPE mRNA levels represented a transient response to brief 5-HT inhibition, additional experiments were performed to provide continual suppression of 5-HT within the striatum. First, rats received daily intraperitoneal injections of saline or the 5-HT1A receptor agonist, 8-OH-DPAT (1 mg/kg), for 7 days to reduce 5-HT release from raphestriatal terminals. In a parallel experiment, the serotonin neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT, 5 micrograms), was stereotaxically injected into the striatum as a means to permanently remove 5-HT terminals. Although levels of each mRNA species were differentially sensitive to 5,7-DHT or 8-OH-DPAT, PPT and PPE mRNAs were lowered between 30-55% within the anterior dorsolateral and ventromedial striatum. Although these results support previous studies suggesting an overall positive regulatory role of serotonin on striatal tachykinin biosynthesis, PPT and PPE gene regulation in certain striatal subregions may by differentially sensitive to lowered 5-HT neurotransmission. This suggestion is supported by observations that acute systemic stimulation of 5-HT2A/C receptors with DOI (7 mg/kg single i.p. injection) raised PPT and PPE mRNA levels within anterior dorsolateral (30-60%) and posterior (100-200%) striata, but not within the anterior ventromedial striatum.

5,7-Dihydroxytryptamine↗

PubMed1996

Thalamocortical afferents in rat transiently express high-affinity serotonin uptake sites.

Autoradiographic techniques using [3H]citalopram were employed in 8-day-old (P-8) and adult rats to delineate the distribution of high-affinity serotonin (5-HT) uptake sites in the cerebral cortex. In the postnatal rats, [3H]citalopram binding sites were densely distributed in the lower portion of layer III, lamina IV, and upper layer V in the primary visual, somatosensory, and auditory cortices. In the primary somatosensory cortex, these binding sites were arrayed in a manner exactly matching the representation of the body surface as demonstrated by other methods such as staining for cytochrome oxidase (CO) or acetylcholinesterase (AChE). In adult rats, there was no differential distribution of [3H]citalopram binding sites in the cerebral cortex. Neonatal administration of the 5-HT neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT), resulted in a nearly complete destruction of the 5-HT innervation of the cortex on P-8, but the patterned distribution of [3H]citalopram binding sites remained visible. In contrast, thalamic lesions carried out on P-4 caused a complete loss of the patterned distribution of [3H]citalopram binding sites in rats killed on either P-5 or P-8. These results are consistent with the conclusion that thalamocortical afferents in postnatal rats transiently express high-affinity uptake sites for 5-HT and thus may accumulate this amine.

5,7-Dihydroxytryptamine↗

PubMed1977

Possible storage of (+)-amphetamine in catecholaminergic terminals of the striatum and brainstem.

6-Hydroxydopamine, given intraventricularly, did not affect the high concentrations of (+)-amphetamine present in the rat striatum and brainstem 1 h after its administration but considerably reduced the small amounts of (+)-amphetamine remaining after 5 h. In contrast, 5,6-dihydroxytryptamine did not modify the (+)-amphetamine concentrations at the times tested. These findings suggest that (+)-amphetamine might be stored in the catecholaminergic but not in the serotonergic central terminals.

5,6-Dihydroxytryptamine↗

PubMed1980

Denervation produces supersensitivity of a serotonergically innervated structure.

The lateral ciliated gill epithelium of Mytilus edulis was denervated physically and chemically with 5,6-dihydroxytryptamine. Lateral ciliary activity which is under excitatory serotonergic control displayed an increased response to superfusion with serotonin after both treatment, as compared to controls. Endogenous serotonin levels were reduced by these treatments. An increase in maximal cilioexcitatory response was also noted.

5,6-Dihydroxytryptamine↗

PubMed1982

A possible mechanism of the tyramine-induced head-twitch response.

The effects of monoaminergic drugs on the head-twitch response (HTR) induced by intracerebroventricular (i.c.v.) injection of tyramine (TyA) in mice pretreated with safrazine, a monoamine oxidase inhibitor, were compared with effects on the response induced by the i.c.v. injection of serotonin (5-HT) in safrazine-pretreated mice. The HTR induced by both TyA and 5-HT were suppressed by i.p. injection of p-chlorophenylalanine. Chlorimipramine enhanced the 5-HT response but not the TyA response. Dimethothiazine, a serotonergic blocker, reduced both the TyA and 5-HT responses. The i.c.v. injection of p-chlorophenylalanine methylester resulted in a reduction of the TyA response but not of the 5-HT response. The i.c.v. injection of 5,6-dihydroxytryptamine (5,6 DHT) 1 day before the test suppressed the TyA response but enhanced the 5-HT response. The i.c.v. injection of noradrenaline reduced both the TyA and 5-HT responses. The i.c.v. injection of 6-hydroxydopamine, and i.p. injection of alpha-methyl-p-tyrosine and tolazoline accelerated the TyA response. These results suggest that the TyA response may be based on the release of endogenous 5-HT and can be suppressed by the catecholaminergic system.

5,6-Dihydroxytryptamine↗

PubMed1982

Serotonin-like actions of quipazine and CPP on spinal motoneurones.

The actions of iontophoretically applied quipazine (QPZ) and 6-chloro-2-[1-piperazinyl]-pyrazine (CPP) were compared with those of serotonin (5-HT) on rat spinal motoneurones. QPZ and CPP qualitatively resembled 5-HT in that both facilitated single unit activity evoked by glutamate. Like 5-HT, the facilitation they produced could be antagonized by metergoline or methysergide. These observations are compatible with the suggestion that the actions of QPZ and CPP are mediated by 5-HT receptors. In rats pretreated with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), QPZ and CPP remained effective in facilitating the glutamate evoked activity, whereas p-chloroamphetamine (PCA), a known releaser of 5-HT, was without effect. In contrast, PCA produced a long lasting facilitation in untreated rats. These data, taken together, suggest that QPZ and CPP are direct agonists at 5-HT receptors, but do not preclude the possibility that they might also act indirectly.

5,7-Dihydroxytryptamine↗

PubMed1983

Phencyclidine-induced stereotyped behaviors in rats following specific neurotoxin lesions of the striatum.

All the components of phencyclidine(PCP)-induced stereotyped behaviors, including sniffing, backpedalling, turning and head weaving were significantly decreased in rats following kainic acid lesion of the striatum. In the 6-hydroxydopamine lesioned rats, the behavioral score of PCP-induced stereotyped sniffing was similar to that in the sham-operated rats, while other components were significantly decreased. In addition, only the PCP-induced backpedalling and head weaving were significantly attenuated in the 5,6-dihydroxytryptamine lesioned rats. These results suggest that not only dopaminergic but also serotonergic and other systems in the striatum may play important roles in PCP-induced stereotyped behaviors.

5,6-Dihydroxytryptamine↗

PubMed1983

[3H]imipramine binding in subcellular fractions of rat cerebral cortex after chemical lesion of serotonergic neurons.

The specific high affinity binding of [3H]imipramine was investigated in subcellular fractions of rat cerebral cortex before and after chemical denervation of serotonergic neurons. In control animals the proportion of the total number of [3H]imipramine binding sites in the nuclear (N), heavy mitochondrial (M), light mitochondrial (L) and microsomal (P) fractions corresponded respectively to 3, 45, 16 and 36% of the total number of binding sites. After chemical lesion of serotonergic neurons with 5,7-dihydroxytryptamine (5,7-DHT) the density of [3H]imipramine binding sites in fractions M and L was decreased by 42 and 52% respectively. In these experiments the uptake of [3H]5-HT in fractions M and L decreased by approximately 80%. The Bmax of [3H]imipramine binding in fraction P was decreased by 80% after chemical denervation with 5,7-DHT. In the control group there was no detectable [3H]5-HT uptake while the endogenous serotonin levels in fraction P were rather low. Our results support the view that the high affinity binding of [3H]imipramine is partly located on serotonergic nerve terminals. The significance of the [3H]imipramine binding sites present in the microsomal (P) fraction remains to be clarified.

5,7-Dihydroxytryptamine↗

PubMed1983

[3H]etorphine binding in rat striatum following lesions of the raphe nuclei.

Following 5,7-dihydroxytryptamine lesions of the rat raphe nuclei a significant reduction in striatal serotonin concentrations was observed. However, with [3H]etorphine as ligand no change in opiate receptor binding was observed in striatal membranes. Moreover, when [3H]etorphine binding was resolved into its mu- and delta + kappa-components no change in either component was observed compared with controls. It is concluded that opiate receptors are not on striatal serotonergic nerve terminals whose cell bodies are located in the raphe nuclei.

5,7-Dihydroxytryptamine↗