Serotonergic Nerve Endings Research Articles

Effects of exercise training on depression and anxiety with changing neurotransmitters in methamphetamine long term abusers: A narrative review

Abstract Study aim: It is generally accepted that methamphetamine (MA) is a highly addictive psychostimulant which copies functions of certain neurotransmitters in the brain, and emits dopamine and serotonin in the brain. Frequent abuse of methamphetamine damages dopaminergic and serotonergic nerve endings at different sites of brain and also increases the anxiety and depression. Exercise seems to reverse physiological and neurological damages due to previous MA dependents and help to reduce anxiety and depression in this population. The aim is to determine the effect of exercise training on neurotransmitters and rate of depression and anxiety in chronic methamphetamine abusers based on a literature review. Materials and methods: The present study investigated published articles in five computerized databases including Magiran, Google scholars, SID, PubMed and Scopus from 2011 until 2020. The searched keywords included sports, neurotransmitter, methamphetamine, depression, anxiety and treatment. The obtained results were described using texts, table and figure. Results: According to the results, physical activity and exercise significantly increased blood serotonin and dopamine levels and significantly decreased the depression and anxiety. Conclusion: Different evidences suggested that physical activity and exercise as positive responses and adaptations might influence on circulatory levels of two neurotransmitters (serotonin and dopamine) in methamphetamine addicts, decrease anxiety and depression, and improve preparation in previous MA dependents. In the rehabilitation period, the overall improvement in previous MA dependents might significantly increase. Exercise training can improve the physical and mental state of people addicted to methamphetamine as a non-drug therapy to promote health. However, more research is necessary to support this conclusion.

Role of Serotonin in Development of Varices in Patients with Cirrhosis

Background and study aim: Serotonin is a one of the monoamine neurotransmitters secreted by serotonergic nerve endings in multiple sites in the brain and gastro-intestinal tract wall. The presence of serotonin receptors on hepatic stellate cells can cause contraction of these cells closing the sinusoidal fenestrae and raising the portal vein pressure. The aim of this work is to study the relation between free serotonin level and the presence of varices in patients with cirrhosis. Patients and Methods: This prospective case control study was carried out on 70 patients with liver cirrhosis attended or admitted to Hepatology Department in Shebein El-Kom Teaching Hospital within the period between May and October 2015. They divided into two groups: Group 1: 40 patients with varices diagnosed by upper GIT endoscopy. Group 2: 30 patients without varices. In addition, 20 healthy persons served as control group (Group 3). All subjects were subjected to full history taking, clinical examination and laboratory investigation including plasma free serotonin by Enzyme Linked Immunosorbant Assay (ELISA). Results: serum serotonin level in group I was significantly higher than group II and control group. Serum serotonin level was significantly correlated to esophageal varices grade, Child, MELD and updated MELD scores. It was also clear that serotonin level rises significantly with higher grades of esophageal varices. Conclusion: Free serotonin had a good power of prediction for development of varices and correlated well with severity of liver disease in patients with cirrhosis assessed by Child, MELD and updated MELD scores as well as OV grade.

Common functional pain syndromes

### Key points When a patient presents with pain of no obvious organic origin, they are often labelled as having ‘functional’ pain. The exact diagnosis is derived from the organ system displaying the predominant symptoms e.g. musculoskeletal pain in fibromyalgia (FM) or visceral pain in irritable bowel syndrome (IBS). The worldwide prevalence of all functional pain syndromes (FPS) is 15–20%. World Health Organization (WHO) surveys reveal that ∼10% of primary care patients develop a chronic pain condition within 12 months of initial registration. Of these, at least 50% continue to have symptoms beyond 1 yr. FPS cause enormous economic burden on society with concurrent ramifications for the individual's family in particular and society in general. FM alone has been estimated to cost around £4000 per patient per year. There has been a paradigm shift in the understanding of FPS. The old model of multiple discrete chronic pain conditions is being replaced by a more overarching, although no less complex, state of central sensitivity syndrome (CSS). Evidence is being accrued that FPS represent the phenotypic output of a complex interplay between genetic susceptibility, gene–environment interactions, and environmental triggers. Four common FPS will be reviewed in this article: FM, IBS, temporomandibular dysfunction (TMD), and chronic cardiac chest pain (CCCP). The pathophysiology and management of each will be examined and the case presented for a shared underlying mechanism called CSS. Once this new mechanism is adopted more widely, it will allow for future novel management options to be …

The Relation between Serum Serotonin and Esophageal Varices in Egyptian Patients with Viral Hepatitis Related Cirrhosis : A Case-Control Study

AIM: Serotonin is a one of the monoamine neurotransmitters secreted by serotonergic nerve endings in multiple sites in the brain and gastrointestinal tract wall. Serotonin can induce contraction in the smooth muscles of the gut wall enhancing gut motility and in blood vessels wall causing vasoconstriction. The presence of serotonin receptors on hepatic stellate cells can cause contraction of these cells closing the sinusoidal fenestrae and raising the portal vein pressure. The aim of this work is to study the relation between serotonin level and the presence and the severity of esophageal varices in Egyptian patients with viral hepatitis related cirrhosis. PATIENTS AND METHODS: Two hundred patients were included in the study group I: 120 patients with viral hepatitis related cirrhosis and group II: 90 healthy volunteers. Patients as well as healthy subjects performed all routine investigations, upper GI endoscopy and serum serotonin level. RESULTS: serum serotonin level in group I was significantly higher than group II (135 ± 33.7 vs 41 ± 19.6). serum serotonin level was significantly correlated to albumin, bilirubin, platelet, portal vein diameter, spleen size, esophageal varices grade, grade of portal hypertensive gastropathy and Child's score (r = -0.35, 0.45, -0.44, 0.5, 0.39, 0.33, 0.36 and 0.41 in succession). It was also clear that serotonin level rises significantly with higher grades of esophageal varices. CONCLUSION: serum serotonin level is significantly correlated to the grade of esophageal varices in patients with viral hepatitis related cirrhosis.

Central Nerve System Symptom of Tri-Cyclic Acids Antidepressants

CNS is the main site of therapeutic action of TCAs and these have direct effects on the CNS. The TCAs antidepressant effect is recognized to be the blockade of monoamine reuptake, at both noradrenergic and serotonergic nerve endings. Tricyclic compounds have anticholinergic effects and predominantly action on myocardium sodium channels then this group has a various symptoms; Since TCA has various presentation; we must ready to find different signs and symptoms of that. We must know all of sign and symptoms to be ready for manage it or them because cannot predict what patients will manifest.

Maternal MDMA administration in mice leads to neonatal growth delay

The psychoactive recreational drug 3,4-methylenedioxymethamphetamine (MDMA) is widely abused. The fact that MDMA induces neurotoxic damage in serotonergic nerve endings is well known. However, the effects of MDMA on pregnant and neonatal animals remain unknown. Therefore, we studied the effects of gestational exposure to MDMA on birth, growth, and behavior of pups. Female BALB/c mice were orally administered either water (10 ml/kg) or MDMA (20 mg/10 ml/kg) from gestational day 1 to postnatal day (P) 21. MDMA did not affect the birth rate, but the survival rate of the pups significantly decreased. A significant reduction in body weight gain was observed in pups from MDMA-administered dams during P3-P21. Maternal MDMA treatment caused an attenuated cliff avoidance reaction and decreased motor function in the pups, as determined by the wire hanging test. These results suggest that MDMA treatment during pregnancy and lactation causes growth retardation and dysfunction of motor neurons in mouse pups.

Recreational drugs, 3,4-Methylenedioxymethamphetamine(MDMA), 3,4-methylenedioxyamphetamine (MDA) and diphenylprolinol, inhibit neurite outgrowth in PC12 cells

3,4-Methylenedioxymethamphetamine (MDMA) is widely abused as a psychoactive recreational drug. It is well known that MDMA induces neurotoxic damage of serotonergic nerve endings. Although drug abuse is increasing among youths, it is unclear whether recreational drugs affect the development of nerve growth. Thus, the present study examined the effect of recreational drugs, such as MDMA, 3,4-methylenedioxyamphetamine (MDA) and diphenylprolinol, a novel recreational drug with a similar chemical structure as that of psychoactive agent pipradrol, on nerve growth factor (NGF)-induced neurite outgrowth. These recreational drugs induced a dose-dependent cell death in PC12 cells. The IC(50) values of MDMA, MDA, R-diphenylprolinol and S-diphenylprolinol were 4.11 mM, 2.75 mM, 1.00 mM and 0.77 mM, respectively, at 24 hr. To examine the effects of these recreational drugs on NGF-induced neurite outgrowth, PC12 cells were treated with NGF together with MDMA, MDA, S-diphenylprolinol or R-diphenylprolinol at low toxic concentrations. The recreational drugs significantly suppressed neurite outgrowth of PC12 cells induced by NGF. The results suggest that these psychoactive recreational drugs may inhibit neurite growth and thus be implicated in their elicited neurotoxicity.

Evidence for a complex influence of nicotinic acetylcholine receptors on hippocampal serotonin release.

The effects of nicotine on 5-hydroxytryptamine (5-HT) release from serotonergic nerve endings in rat dorsal hippocampal slices were studied. Nicotine (50-500 microM:) caused a concentration-dependent increase in 5-HT release. This effect was antagonised by mecamylamine (0.5 microM:), indicating an action at nicotinic receptors. Nicotine-evoked 5-HT release was not affected by tetrodotoxin (3 microM:), cadmium chloride (0.1 mM:), or the absence of Ca(2+) or Na(+) in the superfusion medium. Unexpectedly, higher concentrations of mecamylamine alone (1-50 microM:) increased 5-HT release. This suggested the presence of inhibitory input to 5-HT neurones and that these inhibitory neurones possess tonically active nicotinic receptors. The effect of mecamylamine (50 microM:) on 5-HT release was reduced by the muscarinic M(1) receptor agonist, McN-A-343 (100 microM:), but pirenzepine (0.005-1 microM:), which blocks M(1) receptors, alone increased 5-HT release. Hippocampal serotonergic neurones are known to possess both excitatory nicotinic receptors and inhibitory M(1) receptors. Although there may be several explanations for our results, one possible explanation is that nicotine stimulates 5-HT release by activating nicotinic heteroreceptors on 5-HT terminals. Mecamylamine (0.5 microM:) antagonises this effect, but higher concentrations increase 5-HT release indirectly by blocking the action of endogenous acetylcholine on nicotinic receptors situated on cholinergic neurones that provide muscarinic inhibitory input to 5-HT neurones.

Effect of ecstasy [3,4-methylenedioxymethamphetamine (MDMA)] on cerebral blood flow: a co-registered SPECT and MRI study

3,4-Methylenedioxymethamphetamine (MDMA), an illicit recreational drug, damages serotonergic nerve endings. Since the cerebrovasculature is regulated partly by the serotonergic system, MDMA may affect cerebral blood flow (CBF) in humans. We evaluated 21 abstinent recreational MDMA users and 21 age- and gender-matched healthy subjects with brain SPECT and MRI. Ten of the MDMA subjects also had repeat SPECT and MRI after receiving two doses of MDMA. Abstinent MDMA users showed no significantly different global or regional CBF (rCBF) compared to the control subjects. However, within 3 weeks after MDMA administration, rCBF remained decreased in the visual cortex, the caudate, the superior parietal and dorsolateral frontal regions compared to baseline rCBF. The decreased rCBF tended to be more pronounced in subjects who received the higher dosage of MDMA. Two subjects who were scanned at 2–3 months after MDMA administration showed increased rather than decreased rCBF. Low-dose recreational MDMA use does not cause detectable persistent rCBF changes in humans. The lack of long-term rCBF changes may be due to a non-significant effect of serotonergic deficits on rCBF, or regeneration of serotonergic nerve terminals. The subacute decrease in rCBF after MDMA administration may be due to the direct effect of MDMA on the serotonergic system or the indirect effects of its metabolites on the dopaminergic system; the preliminary data suggest these effects may be transient.

Serotonin via 5‐HT1B and 5‐HT2B receptors stimulates anion secretion in the rat epididymal epithelium

1. The short-circuit current (Isc) technique was used to study the role of 5-hydroxytryptamine (5-HT) in the regulation of anion secretion in cultured rat cauda epididymal epithelia. 2. 5-HT, the 5-HT1B-selective agonist 5-nonyloxytryptamine (5-NOT) and the 5-HT2B-selective agonist alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT) added basolaterally stimulated Isc in a dose-dependent manner with EC50 values of 0.4, 20 and 0.3 microM, respectively. No other agonists for 5-HT receptors had any effect. 3. The pattern of responses to 5-HT was biphasic. Pretreating the tissues with the 5-HT1B-selective antagonist isamoltane (200 microM) and the 5-HT2B-selective antagonist rauwolscine (200 microM) inhibited the rapid transient phase by 55 and 45 %, whereas the sustained phase could only be blocked by rauwolscine. 4. Removal of chloride or bicarbonate or both from the normal Krebs-Henseleit solution reduced the responses to 5-HT, 5-NOT and alpha-methyl-5-HT to varying degrees. The results suggest that 5-HT1B- and 5-HT2B-mediated responses were mainly due to chloride and bicarbonate secretion, respectively. 5. Manipulation of the cAMP and Ca2+ signal transduction pathways with chemical agents provided evidence that the responses to 5-HT were mediated through cAMP. 6. Piroxicam pretreatment abolished the Isc response to alpha-methyl-5-HT but not to 5-NOT, indicating that the 5-HT2B-mediated response, but not the 5-HT1B-mediated response, is dependent on prostaglandin synthesis. 7. Immunohistochemical studies showed that 5-HT-like immunoreactivity was detected in nerve fibres and in small granular cells surrounding the epididymal tubules. 8. It is suggested that the 5-HT released from serotonergic nerve endings and/or from mast cells regulates electrolyte and fluid secretion in the epididymis.

Rat strain differences in the vulnerability of serotonergic nerve endings to neurotoxic damage by p-chloroamphetamine.

Substituted amphetamines are known to selectively destroy serotonin (5-HT) nerve endings in distant projection fields of the dorsal raphe nuclei and the systemic administration of these drugs is widely used in investigations of the role of the central 5-HT system and of the mechanisms involved in their toxicity. Until now Sprague-Dawley rats were almost exclusively used for this purpose and the findings were thought to apply to other strains as well. We compared the long-term effects of the administration of different doses of para-chloroamphetamine (PCA) on three specific markers of the density of 5-HT presynapses, [3H]-paroxetine binding to 5-HT-transporters, tryptophan hydroxylase apoenzyme contents, and 5-HT levels in the frontal cortex of Sprague-Dawley and Wistar rats. PCA-treatment caused a dose dependent decline of all three parameters which was much more pronounced in Sprague-Dawley compared to Wistar rats. An i.p. dose of 4 mg PCA/kg body weight, which caused a severe, about 90% reduction of all three parameters of 5-HT innervation in Sprague-Dawley rats was almost ineffective in Wistar rats. The dose of 8 mg/kg which was required to eliminate about 80% of cortical 5-HT presynapses in Wistar rats was already lethal to Sprague-Dawley rats. The reasons of this different susceptibility of the 5-HT system in the two rat strains are unknown. Their elucidation will contribute to a better understanding of inherited differences in individual vulnerability to the neurotoxic effects of substituted amphetamines. The combined measurements of transporter density, of tryptophan hydroxylase apoenzyme contents, and of 5-HT levels is a powerful tool for the assessment of experimentally induced changes in the density of 5-HT innervation in distant projection fields of the raphe nuclei.

Simultaneous assay of platelet and plasma catecholamines by HPLC with coulometric detection

Platelets and monoaminergic neurons share many morphological, biochemical, and pharmacological properties. In addition to its similarities to serotonergic nerve endings, the platelet has also been considered a good model for the study of the noradrenergic function, since it can selectively take up, store, and release norepinephrine (NE).

Microinjection of propranolol into the dorsal periaqueductal gray causes an anxiolytic effect in the elevated plus-maze antagonized by ritanserin

The 5-HT1A/1B receptor antagonist propranolol was injected into the dorsal periaqueductal gray (DPAG) of rats exposed to the elevated plus-maze in order to investigate the participation in anxiety of 5-HT mechanisms operating in this brain region. Microinjection of D,L- or L-propranolol into the DPAG increased the percentage of total arm entries without affecting the total number of entries into either open or enclosed arms of the maze, an effect characteristic of anxiolytic drugs injected systemically. The doses of 5 nmol L-propranolol and 10 nmol D,L-propranolol caused anxiolytic effects of comparable magnitude, while the doses of 2.5 nmol of the former and 5 nmol of the latter were ineffective. Therefore, the L-isomer is likely to be the main one responsible for the pharmacological activity observed. In addition, the anxiolytic effect of 10 nmol D,L-propranolol was antagonized by 10 nmol of the 5-HT2/1C receptor antagonist ritanserin, previously injected into the DPAG. The present as well as previously reported results suggest that the anxiolytic effect of propranolol injected into the DPAG is due to increased release of 5-HT acting on post-synaptic 5-HT2 receptors, resultant from blockade of 5-HT1B autoreceptors that inhibit amine release from serotonergic nerve endings.

Neural control of swimming in Aplysia brasiliana. III. Serotonergic modulatory neurons.

1. We describe a group of serotonergic neurons in the pedal ganglia of Aplysia brasiliana and characterize their modulatory effects on the motoneuron input to swimming muscles of the parapodia. Each pedal ganglion contains one cluster of large neurons near its dorsomedial surface that fires in phase with opening (downstroke) of the parapodia; these have been designated parapodial opener-phase (POP) cells. 2. POP cells are large, number 15-20 per ganglion, have peripheral axons in parapodial nerves, have distinctively shaped action potentials, and fire in bursts phasically with motoneurons during the opening, or downstroke portion, of parapodial movement during fictive swimming. Firing individual POP cells with intracellular current indicates that they have no direct detectable effect on muscle, causing neither junction potentials nor contractions. 3. 5,7-Dihydroxytryptamine (5,7-DHT) staining, immunocytochemistry using serotonin (5-HT) antibodies, and direct biochemical measurements revealed that POP cells are serotonergic. Serotonergic nerve endings were also seen in parapodial muscle. 4. Simultaneous intracellular recordings and use of altered divalent concentrations revealed that no detectable direct synaptic interactions exist between POP cells and motor neurons. 5. When POP cells and motoneurons were simultaneously recorded while measuring muscle contractions, it was found that POP cell activity enhances motoneuron-induced tension by 120-900%, averaging around 300%. Variability in the efficacy of individual POP cells suggests that they may influence specific regions or groups of muscle fibers. 6. POP cell activity also significantly increased the rate of relaxation of parapodial muscle contractions, averaging about a 40% reduction in the time required to relax to one-half peak tension. Increased relaxation rate implies a postsynaptic change in muscle behavior. 7. The effectiveness of POP cells to increase contraction tension and relaxation rate was positively correlated with POP cell spike frequency. These effects were slow (seconds) in onset and could persist for a minute or more after cessation of POP firing. Concurrent motoneuron activity is not required for modulation by POP cells. 8. Simultaneous intracellular recording from a POP cell, motoneuron, and muscle fiber revealed that POP cell activity enhanced the amplitude of motoneuron-induced excitatory junction potentials (EJPs). Activity of POP cells did not alter muscle fiber membrane potential, but the experiments left open the possibility that EJP enhancement is presynaptic, postsynaptic, or a combination.(ABSTRACT TRUNCATED AT 400 WORDS)

Serotonergic denervation does not reduce brain uptake of n-Isopropyl- p-[ 123I]iodoamphetamine in vivo

The relation between brain uptake of radiolabeled n-isopropyl- p-iodoamphetamine ([ 123I]IMP) and serotonin re-uptake sites was studied in vivo by lesioning serotonergic nerve endings. The reduction of brain serotonin demonstrated the effectiveness of the procedure. Accumulation of radioactivity/g brain tissue was higher in the lesioned than in the sham-operated rats. This was explained by the loss of body weight of the lesioned animals, allowing an increased distribution to the brain. These results demonstrate that the in vivo distribution and binding of [ 123I]IMP in the brain is not limited to the specific serotonin re-uptake sites on nerve endings.

Activation of A1 adenosine receptors decreases the release of serotonin in the rabbit hippocampus, but not in the caudate nucleus.

The effects of A1 adenosine receptor ligands on the evoked release of serotonin (5-HT) were studied in slices of the hippocampus and the caudate nucleus of the rabbit, preincubated with 3H-5-HT. In hippocampal tissue electrical stimulation elicited a release which was inhibited by the adenosine receptor agonist N6-cyclohexyladenosine (CHA) and enhanced by the selective A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). The concentration-response curve of CHA was shifted to the right by DPCPX. The shift corresponded to a pA2 value of 9.4 for DPCPX. CHA, R-N6-phenylisopropyladenosine (R-PIA) and DPCPX were ineffective in caudate nucleus tissue. When instead of electrical pulses high K+ was used to induce 5-HT release in the presence of the Na+ channel blocker tetrodotoxin (TTX), which was present in order to exclude effects mediated by interneurones, CHA was equally effective in the hippocampus but again failed to modify 5-HT release in the caudate nucleus. The disinhibition by DPCPX of the evoked 5-HT release was used to calculate the extracellular concentration of endogenous adenosine at the A1 receptor. The calculation greatly depended on the dissociation constant of adenosine at the A1 receptor. It is concluded that A1 adenosine receptors, activated by the endogenous agonist at a concentration of about 0.7 mumol/l, are located on serotonergic nerve endings in the hippocampus, but not in the caudate nucleus. The estimated extracellular concentration of endogenous adenosine is in reasonable agreement with actually measured concentrations reported in the literature.

Presynaptic Serotonergic Dysfunction in Patients with Alzheimer's Disease

Indices of presynaptic serotonergic nerve endings were assayed in neocortical biopsy samples from patients with histologically verified Alzheimer's disease. The concentrations of 5-hydroxytryptamine (serotonin) and 5-hydroxyindoleacetic acid, serotonin uptake, and K+-stimulated release of endogenous serotonin were all found to be reduced below control values. Changes occurred in samples from both the frontal and temporal lobes, but they were most severe (at least a 55% reduction) in the temporal lobe. This is indicative of substantial serotonergic denervation. Values for serotonergic markers in Alzheimer's disease samples did not show correlations with rating of the severity of dementia, indices of cholinergic innervation, or senile plaque and cortical pyramidal neurone loss. However, neurofibrillary tangle count and an index of glucose oxidation (both probably reflecting pyramidal cells) correlated with the concentration of 5-hydroxyindoleacetic acid.

3H-5-hydroxytryptamine accumulation by rat brain synaptic vesicles in a membrane-impermeant medium, and selective reduction by 5,7-dihydroxytryptamine.

In order to examine possible selectivity of amine uptake by synaptic vesicles, the ATP-stimulated accumulation of 3H-5-hydroxytryptamine (5HT) by synaptic vesicles from rat whole brain was examined in a medium comprised largely of membrane-impermeant anions (d-tartrate). Such media have previously been shown to stabilize vesicular accumulation of several neurotransmitters. Accumulation of 3H-5HT did not occur in tartrate medium alone, but was increased biphasically with increasing concentrations of both potassium phosphate and potassium bicarbonate. At optimal concentrations of each anion (10 mM), stable accumulation of 3H-5HT was observed at 37 degrees (26.1 +/- 1.2 pmol/mg protein; Km 6 X 10(-7) M), which was reduced by greater than 95% in the absence of K2ATP, at 4 degrees C, in the presence of 10(-6) M reserpine, or in the presence of the proton ionophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP). Uptake was significantly antagonized by millimolar concentrations of Na+, Mg++ or Cl-, but was unaffected by ouabain (10(-5) M). Pretreatment of animals with 5,7-dihydroxytryptamine (5,7-DHT) (200 micrograms, intraventricular) 10 days prior to sacrifice reduced endogenous 5HT levels by 70%, while levels of endogenous norepinephrine (NE) and dopamine (DA) were unaffected. Accumulation of 3H-5HT, examined in the presence of 10(-6) M NE to block 3H-5HT accumulation by vesicles from noradrenergic nerve endings, was reduced by 40% in vesicles from treated animals. Vesicular accumulation of 3H-(-)-NE and 3H-DA was unaffected by 5,7-DHT treatment. The data suggest the possibility of preferential accumulation of 3H-5HT by vesicles arising from serotonergic nerve endings.

High-affinity uptake of serotonin into immunocytochemically identified astrocytes.

Primary cultures of astrocytes from neonatal rat brain were incubated with tritiated serotonin. After fixation they were stained by immunofluorescence for the astrocyte-specific marker glial fibrillary acidic protein and processed for autoradiography. Silver grain density was increased over cells positive for glial fibrillary acidic protein and was reduced to background levels when sodium was omitted from the medium or the specific inhibitors of serotonin uptake fluoxetine and chlorimipramine were present. The results indicate that mammalian astrocytes can take up serotonin by a sodium-dependent, high-affinity system previously thought to be the exclusive property of serotonergic nerve endings.

Release and inhibition of uptake of 5-hydroxytryptamine in blood platelets in vitro by copper and methyl mercury.

Divalent copper (Cu) and methyl mercury (Met-Hg) are potent inhibitors of the uptake of 5-hydroxytryptamine (5-HT) in rat hypothalamic synaptosomes in vitro. To assess the usefulness of blood platelets as a peripheral model of central serotonergic nerve endings for neurotoxicological studies, for comparison human and rabbit platelets were utilized. Cu inhibited 5-HT uptake into human platelets when platelets were separated from plasma (the IC50 0.7-0.8 microM). Plasma added with platelets abolished the toxic influence of Cu towards platelets. Met-Hg inhibited 5-HT uptake both in washed platelets (the IC50 0.2 microM) and in platelets added in plasma (the IC50s 10-15 microM). The inhibition of uptake by Met-Hg did not depend on buffer Ca and Mg. At low concentrations of Cu, the uptake tended to be more inhibited in the presence of Ca and Mg. Zn and Hg did not affect 5-HT uptake up to 100 microM. Pb inhibited it transiently (28% at 1 microM) in the presence of Ca and Mg. Met-Hg induced the release of endogenous 5-HT from rabbit platelets when they were in a suspension in Ca-free buffer, but Cu did not, even at 100 microM concentration. The results suggest firstly, that blood platelets give results comparable with brain synaptosomes regarding inhibitory effects of metals on 5-HT uptake provided plasma is decanted. Secondly, the inhibition of 5-HT uptake by Cu appears to be purely plasma membrane related but Met-Hg may, in addition, induce release of 5-HT from storage granules.