First-in-Class Selenium-Containing Potent Serotonin Receptor 5-HT6 Agents with a Beneficial Neuroprotective Profile against Alzheimer's Disease.

Alzheimer's disease (AD) has a complex and not-fully-understood etiology. Recently, the serotonin receptor 5-HT6 emerged as a promising target for AD treatment; thus, here a new series of 5-HT6R ligands with a 1,3,5-triazine core and selenoether linkers was explored. Among them, the 2-naphthyl derivatives exhibited strong 5-HT6R affinity and selectivity over 5-HT1AR (13-15), 5-HT7R (14 and 15), and 5-HT2AR (13). Compound 15 displayed high selectivity for 5-HT6R over other central nervous system receptors and exhibited low risk of cardio-, hepato-, and nephrotoxicity and no mutagenicity, indicating its "drug-like" potential. Compound 15 also demonstrated neuroprotection against rotenone-induced neurotoxicity as well as antioxidant and glutathione peroxidase (GPx)-like activity and regulated antioxidant and pro-inflammatory genes and NRF2 nuclear translocation. In rats, 15 showed satisfying pharmacokinetics, penetrated the blood-brain barrier, reversed MK-801-induced memory impairment, and exhibited anxiolytic-like properties. 15's neuroprotective and procognitive-like effects, stronger than those of the approved drug donepezil, may pave the way for the use of selenotriazines to inhibit both causes and symptoms in AD therapy.

Brown Slime Cap Mushroom (Chroogomphus rutilus, Agaricomycetes) Polysaccharide Resists Motion Sickness by Inhibiting the Activity of the Serotonin System in Mice.

Motion sickness (MS) is a disorder of the autonomic nervous system caused by abnormal exercise with symptoms such as nausea, vomiting and drowsiness. More than 90% of the human population has experienced different degrees of MS. At present, anticholinergics, antihistamines, and sympathomimetic drugs are used for treating MS, but these drugs generally have some adverse reactions and are not suitable for all people. Therefore, it is necessary to develop anti-MS drugs that have high efficiency and no adverse effects. Previous studies have found that Chroogomphus rutilus polysaccharide (CRP) is effective at preventing and treating MS in rats and mice. However, its mechanism of action is not clear. To clarify whether the CRP has anti-MS effects in mice, and to clarify its mechanism, we performed behavioral, biochemical, and morphological tests in a Kunming mouse model. Our results indicate that CRPs can significantly relieve the symptoms of MS, and their effect is equivalent to that of scopolamine, a commonly used anti-MS medicine. Our results indicate that CRPs may directly act on the gastrointestinal chromaffin cells to inhibit the synthesis and release of serotonin (5-hydroxytryptamine, or 5-HT) and thus reduce the signal from the gastrointestinal tract.

Exploring the mechanism of traditional Chinese medicine in regulating gut-derived 5-HT for osteoporosis treatment.

Osteoporosis is a systemic bone disease characterized by an imbalance in the relationship between osteoblasts, osteocytes, and osteoclasts. This imbalance in bone metabolism results in the destruction of the bone's microstructure and an increase in bone brittleness, thereby increasing the risk of fractures. Osteoporosis has complex causes, one of which is related to the dysregulation of 5-hydroxytryptamine, a neurotransmitter closely associated with bone tissue metabolism. Dysregulation of 5-HT directly or indirectly promotes the occurrence and development of osteoporosis. This paper aims to discuss the regulation of 5-HT by Traditional Chinese Medicine and its impact on bone metabolism, as well as the underlying mechanism of action. The results of this study demonstrate that Traditional Chinese Medicine has the ability to regulate 5-HT, thereby modulating bone metabolism and improving bone loss. These findings provide valuable insights for future osteoporosis treatment.

Theabrownin inhibits obesity and non-alcoholic fatty liver disease in mice via serotonin-related signaling pathways and gut-liver axis.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) with obesity seriously threats public health. Our previous studies showed that dark tea had more potential on regulating lipid metabolism than other teas, and theabrownin (TB) was considered to be a main contributor to the bioactivity of dark tea. OBJECTIVES: This in vivo study aims to reveal the effects and molecular mechanisms of TB on NAFLD and obesity, and the role of the gut-liver axis is explored. METHODS: The histopathological examinations, biochemical tests, and nuclear magnetic resonance were applied to evaluate the effects of TB on NAFLD and obesity. The untargeted metabolomics was used to find the key molecule for further exploration of molecular mechanisms. The 16S rRNA gene sequencing was used to assess the changes in gut microbiota. The antibiotic cocktail and fecal microbiota transplant were used to clarify the role of gut microbiota. RESULTS: TB markedly reduced body weight gain (67.01%), body fat rate (62.81%), and hepatic TG level (51.35%) in the preventive experiment. Especially, TB decreased body weight (32.16%), body fat rate (42.56%), and hepatic TG level (42.86%) in the therapeutic experiment. The mechanisms of action could be the improvement of fatty acid oxidation, lipolysis, and oxidative stress via the regulation of serotonin-related signaling pathways. Also, TB increased the abundance of serotonin-related gut microbiota, such as Akkermansia, Bacteroides and Parabacteroides. Antibiotics-induced gut bacterial dysbiosis disrupted the regulation of TB on serotonin-related signaling pathways in liver, whereas the beneficial regulation of TB on target proteins was regained with the restoration of gut microbiota. CONCLUSION: We find that TB has markedly preventive and therapeutic effects on NAFLD and obesity by regulating serotonin level and related signaling pathways through gut microbiota. Furthermore, gut microbiota and TB co-contribute to alleviating NAFLD and obesity. TB could be a promising medicine for NAFLD and obesity.

Effect of Shugan Jianpi Recipe Combined with Cross Moxibustion on Biochemical Examination Indexes and Total Score of TCM Symptoms in Patients with Spleen-Stomach Damp-Heat Diarrhea Irritable Bowel Syndrome.

Objective: To explore the effect of Shugan Jianpi recipe combined with cross moxibustion on biochemical examination indexes and total score of TCM symptoms in patients with spleen-stomach damp-heat diarrhea irritable bowel syndrome (IBS). Methods: Sixty patients with spleen-stomach damp-heat diarrhea (IBS) treated in our hospital from January 2019 to September 2021 were enrolled. The patients were randomly assigned into the control group and study group. The control group was treated with Chang Shugan Jianpi recipe, and the study group was treated with Shugan Jianpi recipe combined with cross moxibustion. The curative effect, single symptom score, total score of TCM clinical symptoms, plasma gastrointestinal hormone level, IBS-QOL score, and recurrence were compared. Results: First of all, we compared the curative effects. The study group was significantly effective in 24 cases, effective in 5 cases, and ineffective in 1 case, and the effective rate was 96.67%. In the control group, 13 cases were markedly effective, 10 cases were effective, and 7 cases were ineffective, and the effective rate was 76.67%. The effective rate of the study group was higher compared to the control group (P < 0.05). Secondly, the individual symptom scores were compared. Compared between the two groups, the scores of diarrhea times, stool characteristics, abdominal pain, and abdominal distension in the study group were lower compared to the control group (P < 0.05). After treatment, the total score of TCM clinical symptoms decreased. Compared between the two groups, the total score of TCM clinical symptoms in the study group was lower compared to the control group at 1 week, 2 weeks, and 4 weeks after treatment (P < 0.05). After treatment, the levels of 5-HT and VIP decreased. The levels of 5-HT and VIP in the study group were lower compared to the control group (P < 0.05). The scores of anxieties, health worry, behavioral disorder, social reaction, somatic intention, interpersonal relationship, dietary concern, and sexual behavior in the study group were lower compared to the control group. The IBS-QOL scores were significantly lower compared to the control group (P < 0.05). Finally, we compared the recurrence. The recurrence rate in the study group was lower compared to the control group (P < 0.05). Conclusion: The prescription combined with cross moxibustion has the effect of soothing the liver and invigorating the spleen, resolving dampness and stomach, and can reduce the main clinical symptoms of patients with diarrhea IBS of spleen-stomach damp-heat type, and the overall effect is significant. It can also enhance the emotional state of anxiety and depression and achieve the overall psychological and physical balance and health state, and the recurrence rate is low, which can be further applied in clinic.

The Role of Natural Products in Treatment of Depressive Disorder.

Depressive disorder is one of the most common psychiatric syndromes that, if left untreated, can cause many disturbances in a person's life. Numerous factors are involved in depression, including inflammation, brain-derived neurotrophic factor (BDNF), GABAergic system, hypothalamic- pituitary-adrenal (HPA) Axis, monoamine neurotransmitters (serotonin (5-HT), noradrenaline, and dopamine). Common treatments for depression are selective serotonin reuptake inhibitors, tricyclic antidepressants, and monoamine oxidase inhibitors, but these drugs have several side effects such as anxiety, diarrhea, constipation, weight loss, and sexual dysfunctions. These agents only reduce the symptoms and temporarily reduce the rate of cognitive impairment associated with depression. As a result, extensive research has recently been conducted on the potential use of antidepressant and sedative herbs. According to the available data, herbs used in traditional medicine can be significantly effective in reducing depression, depressive symptoms and improving patients' performance. The present study provides a summary of biomarkers and therapeutic goals of depression and shows that natural products such as saffron or genipin have antidepressant effects. Some of the useful natural products and their mechanisms were evaluated. Data on various herbs and natural isolated compounds reported to prevent and reduce depressive symptoms is also discussed.

Phytochemistry and Pharmacology of Carthamus tinctorius L.

Carthamus tinctorius L. is a multifunctional cash crop. Its flowers and seeds are extensively used in traditional herbal medicine in China, Korea, Japan, and other Asian countries, for treating various ailments such as gynecological, cardiovascular, and cerebrovascular diseases as well as blood stasis and osteoporosis. More than 100 compounds have been isolated and identified from C. tinctorius. Flavonoids and alkaloids, especially the quinochalcone c-glycoside hydroxysafflor yellow A, N-(p-Coumaroyl)serotonin, and N-feruloylserotonin, are responsible for most of the pharmacological activities of C. tinctorius. In this paper, comprehensive and up-to-date information on the phytochemistry and pharmacology of C. tinctorius is presented. This information will be helpful for further explorations of the therapeutic potential of C. tinctorius and may provide future research opportunities.

Therapeutic benefits of a component of coffee in a rat model of Alzheimer's disease.

A minor component of coffee unrelated to caffeine, eicosanoyl-5-hydroxytryptamide (EHT), provides protection in a rat model for Alzheimer's disease (AD). In this model, viral expression of the phosphoprotein phosphatase 2A (PP2A) endogenous inhibitor, the I2(PP2A), or SET protein in the brains of rats leads to several characteristic features of AD including cognitive impairment, tau hyperphosphorylation, and elevated levels of cytoplasmic amyloid-ß protein. Dietary supplementation with EHT for 6-12 months resulted in substantial amelioration of all these defects. The beneficial effects of EHT could be associated with its ability to increase PP2A activity by inhibiting the demethylation of its catalytic subunit PP2Ac. These findings raise the possibility that EHT may make a substantial contribution to the apparent neuroprotective benefits associated with coffee consumption as evidenced by numerous epidemiologic studies indicating that coffee drinkers have substantially lowered risk of developing AD.

Oxidative stress mediated neuronal damage in the corpus striatum of 6-hydroxydopamine lesioned Parkinson's rats: neuroprotection by serotonin, GABA and bone marrow cells supplementation.

Oxidative stress-induced neuronal cell death has been implicated in Parkinson's disease (PD). Oxidative stress initiated by 6-hydroxydopamine (6-OHDA) causes mitochondrial dysfunction leading to apoptosis and Parkinsonian neurodegeneration. We investigated the neuroprotective potential of serotonin (5-HT), gamma amino butyric acid (GABA) and autologous bone marrow cells (BMC) in combination against oxidative stress-induced cell death. PD was induced in adult male Wistar rats by intranigral infusion of 6-OHDA (8 µg/µl). The activities of antioxidant enzymes--superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were analysed. The extent of lipid peroxidation was quantified by measuring the formation of thiobarbituric acid reactive substances (TBARs). Real Time PCR gene expression of SOD, CAT and GPx were performed using specific Taqman probes. 6-OHDA induced decreased activity of SOD, CAT and GPx in corpus striatum was significantly reversed to near control (p<0.001) by treatment with 5-HT, GABA and bone marrow cells. Gene expression studies of SOD, CAT and GPx using Real Time PCR confirmed the above observation. TBAR levels were elevated (p<0.001) in 6-OHDA treated rats indicating lipid peroxidation. 5-HT and GABA along with autologous bone marrow cell supplementation significantly ameliorated 6-OHDA-induced lipid peroxidation (p<0.001). Our results suggest a new therapeutic strategy of neuroprotection against damage by oxidative stress in Parkinson's disease.

Role of serotonin in Alzheimer's disease: a new therapeutic target?

Mounting evidence accumulated over the past few years indicates that the neurotransmitter serotonin plays a significant role in cognition. As a drug target, serotonin receptors have received notable attention due in particular to the role of several serotonin-receptor subclasses in cognition and memory. The intimate anatomical and neurochemical association of the serotonergic system with brain areas that regulate memory and learning has directed current drug discovery programmes to focus on this system as a major therapeutic drug target. Thus far, none of these programmes has yielded unambiguous data that suggest that any of the new drug entities possesses disease-modifying properties, and significantly more research in this promising area of investigation is required. Compounds are currently being investigated for activity against serotonin 5-HT(1), 5-HT(4) and 5-HT(6) receptors. This review concludes that most work done in the development of selective serotonin receptor ligands is in the pre-clinical or early clinical phase. Also, while many of these compounds will likely find application as adjuvant therapy in the symptomatic treatment of Alzheimer's disease, there are currently only a few drug entities with activity against serotonin receptors that may offer the potential to alter the progression of the disease.

Folic acid supplementation as adjunctive treatment premature ejaculation.

Selective serotonin re-uptake inhibitors (SSRIs), has been increasingly used for the treatment of premature ejaculation over the past 5 years. It was reported that folic acid plays important roles in synthesis of 5-HT. Therefore, we hypothesize that folic acid supplementation may cures premature ejaculation by the same mechanism of interacting with monoamine neurotransmitters in brain, to be the replacement of RRSIs. Folic acid supplementation cures premature ejaculation more safely. These new views will help to understand the diagnosis and treatment methods for premature ejaculation.

The dual fatty acid amide hydrolase/TRPV1 blocker, N-arachidonoyl-serotonin, relieves carrageenan-induced inflammation and hyperalgesia in mice.

Given that the pharmacological or genetic inactivation of fatty acid amide hydrolase (FAAH) counteracts pain and inflammation, and on the basis of the established involvement of transient receptor potential vanilloid type-1 (TRPV1) channels in inflammatory pain, we tested the capability of a dual FAAH/TRPV1 blocker, N-arachidonoyl-serotonin (AA-5-HT), to relieve oedema and pain in a model of acute inflammation, and compared its efficacy with that of a single FAAH inhibitor (URB597) or TRPV1 antagonist (capsazepine). Acute inflammation was induced by intraplantar injection of lambda-carrageenan into mice and the anti-inflammatory and anti-nociceptive actions of AA-5-HT were assessed at different doses, time points and treatment schedule. In addition, endocannabinoid levels were measured in paw skin and spinal cord. Systemic administration of AA-5-HT elicited dose-dependent anti-oedemigen and anti-nociceptive effects, whereas it was devoid of efficacy when given locally. When tested in a therapeutic regimen, the compound retained comparable anti-inflammatory effects. TRPV1 receptor mediated the anti-inflammatory property of AA-5-HT, whereas both CB(1) and TRPV1 receptors were involved in its anti-hyperalgesic activity. These effects were accompanied by an increase of the levels of the endocannabinoid anandamide (AEA) in both inflamed paw and spinal cord. AA-5-HT was more potent than capsazepine as anti-oedemigen and anti-hyperalgesic drug, whereas it shows an anti-oedemigen property similar to URB597, which was, however, devoid of the anti-nociceptive effect. AA-5-HT did not induce unwanted effects on locomotion and body temperature. In conclusion AA-5-HT has both anti-inflammatory and anti-hyperalgesic properties and its employment offers advantages, in terms of efficacy and lack of adverse effects, deriving from its dual activity.

Pain relief by spinal cord stimulation involves serotonergic mechanisms: an experimental study in a rat model of mononeuropathy.

The aim of the present study was to examine the role of the spinal serotonergic system in the pain relieving effect of spinal cord stimulation (SCS) using a rat model of mononeuropathy. Tactile withdrawal thresholds, cold responses and heat withdrawal latencies were assessed before and after SCS. In some rats, SCS produced an attenuation of the hypersensitivity following nerve injury (SCS responding rats). When SCS was applied immediately prior to sacrifice, the 5-HT content in the dorsal quadrant of the spinal cord ipsilateral to the nerve injury was increased in SCS responding rats. But there was no change in responding rats without stimulation, or in SCS non-responding rats with or without stimulation or in controls. Immunohistochemical examination showed a high density of 5-HT stained terminals in the dorsal horn superficial laminae (I-II) in SCS responding rats following stimulation. It was also found that i.t. administration of a sub-effective dose of serotonin in SCS non-responding rats markedly enhanced the pain relieving effect of SCS on tactile and cold hypersensitivity, while there was no effect on heat hyperalgesia. This enhanced effect on tactile hypersensitivity could be partially blocked by a GABA(B) receptor antagonist (CGP 35348) but not by a muscarinic M(4) receptor antagonist (Muscarinic toxin 3) administered i.t. shortly before the 5-HT injection. In conclusion, there is evidence that the spinal 5-HT system plays an important role in the mode of action of SCS involving the activation of descending serotonergic pathways that may inhibit spinal nociceptive processing partially via a GABAergic link.

Safflower seed polyphenols (N-(p-coumaroyl)serotonin and N-feruloylserotonin) ameliorate atherosclerosis and distensibility of the aortic wall in Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits.

Pulse wave velocity (PWV) has been used clinically as a direct measure of arterial stiffness. We investigated the inhibitory effects of defatted safflower seed extract (SSE) and serotonin derivatives (N-(p-coumaroyl)serotonin, N-feruloylserotonin; CS+FS), which are the active components in SSE, on hypercholesterolemia and atherosclerosis, using PWV in Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits. SSE and CS+FS were supplemented with a commercial diet containing 0.5% cholesterol for 8 weeks in male KHC rabbits, aged 2 months. Pulse waves were recorded at different aortic positions using two catheters with micromanometers under pentobarbital anesthesia. The atherosclerotic lesioned area in the aorta was significantly reduced in the SSE and CS+FS groups, without significant changes in serum cholesterol and triglyceride levels among the three groups after supplementation. Local PWV (LPWV) in the middle thoracic and distal abdominal aortas was significantly smaller in the SSE and CS+FS groups than in the control group. PWV in the entire aorta was also significantly lower in the SSE and CS+FS groups, compared with that in the control group. Pressure-strain elastic modulus, an index of wall distensibility, was significantly lower in the middle thoracic and middle abdominal aortas in the SSE and CS+FS groups than in the control group. Wall thickness was also significantly smaller in the middle thoracic aorta in the SSE and CS+FS groups compared with that in the control group. Serotonin derivatives inhibited the progress of atherosclerosis and ameliorated wall distensibility, which contributed, in part, to the lowering of LPWV. Serotonin derivatives may be beneficial in improving vascular distensibility and in reducing cardiovascular risk.

Anticonvulsant serotonergic and deep brain stimulation in anterior thalamus.

OBJECTIVE: Anterior thalamus (AN) has been shown to mediate seizures in both focal and generalized models. Specific regional increase in AN serotonergic activity was observed following AN-DBS in our pentylenetetrazol (PTZ) rodent model of acute seizures, and this increase may inhibit seizures and contribute to the mechanism of anticonvulsant DBS. METHODS: Anesthetized rats with AN-directed dialysis cannula with scalp/depth EEG were infused with PTZ at 5.5mg/(kg min) until an EEG seizure occurred. Eight experimental groups of AN-dialysis infusion were evaluated: controls (dialysate-only), 10 and 100 microM serotonin 5-HT(7) agonist 5-carboxamidotryptamine (5-CT), 1, 10 and 100 microM serotonin antagonist methysergide (METH), AN-DBS, and 100 microM METH+AN-DBS. RESULTS: Latency for seizures in control animals was 3,120+/-770 s (S.D.); AN-DBS delayed onset to 5018+/-1100 (p<0.01). AN-directed 5-CT increased latency in dose-dependent fashion: 3890+/-430 and 4247+/-528 (p<0.05). Methysergide had an unexpected protective effect at low-dose (3908+/-550, p<0.05) but not at 100 microM (2687+/-1079). The anticonvulsant action of AN-DBS was blocked by prior dialysis using 100 microM METH. Surface EEG burst count and nonlinear analysis (H-Statistic) noted significant (p<0.05) increased pre-ictal epileptiform bursts in 5-CT, methysergide, but not DBS group compared to control. CONCLUSION: Increased serotonergic activity in AN raised PTZ seizure threshold, similar to DBS, but without preventing cortical bursting. 5-Carboxamidotryptamine, a 5-HT(7) agonist, demonstrated dose-dependent seizure inhibition. Methysergide proved to have an inverse, dose-dependent agonist property, antagonizing the action of AN-DBS at the highest dose. Anticonvulsant AN-DBS may in part act to selectively alter serotonin neurotransmission to raise seizure threshold.

Up-regulation of anandamide levels as an endogenous mechanism and a pharmacological strategy to limit colon inflammation.

Direct stimulation of cannabinoid CB1 receptors exerts a protective function in animal models of inflammatory bowel diseases (IBDs). However, it is not known whether endocannabinoids are up-regulated during IBDs in animals or humans, nor whether pharmacological elevation of endocannabinoid levels can be exploited therapeutically in these disorders. In this study we addressed these questions. Colon inflammation was induced in mice and rats with 2,4-dinitrobenzene- and 2,4,6-trinitrobenzene sulfonic acids (DNBS and TNBS), respectively. DNBS-treated mice were treated chronically (for 3 or 7 days) with inhibitors of anandamide enzymatic hydrolysis (N-arachidonoyl-serotonin, AA-5-HT) or reuptake (VDM11), 10 or 5 mg/kg, s.c., or with 5-amino-salicilic acid (5-ASA, 1.4 mg/kg, i.r.). Endocannabinoids (anandamide and 2-arachidonoylglycerol, 2-AG) were quantified in mouse colon, or in rat colon mucosa and submucosa, and in bioptic samples from the colon of patients with untreated ulcerative colitis, by liquid chromatography-mass spectrometry. A strong elevation of anandamide, but not 2-AG, levels was found in the colon of DNBS-treated mice, in the colon submucosa of TNBS-treated rats, and in the biopsies of patients with ulcerative colitis. VDM-11 significantly elevated anandamide levels in the colon of DNBS-treated mice and concomitantly abolished inflammation, whereas AA-5-HT did not affect endocannabinoid levels and was significantly less efficacious at attenuating colitis. 5-ASA also increased anandamide levels and abolished colitis. Thus, anandamide is elevated in the inflamed colon of patients with ulcerative colitis, as well as in animal models of IBDs, to control inflammation, and elevation of its levels with inhibitors of its cellular reuptake might be used in the treatment of IBDs.

Induction of prolonged tenderness in patients with tension-type headache by means of a new experimental model of myofascial pain.

Tenderness is the most prominent abnormal finding in patients with tension-type headache (TTH). Recently we developed a model of myofascial tenderness using intramuscular infusion of a combination of bradykinin, serotonin, histamine and prostaglandin E2. We aimed to examine tenderness after this combination in patients with episodic TTH (ETTH). Fifteen patients and 15 healthy controls completed the study. Participants received the combination into the non-dominant trapezius muscle in a randomized, double-blinded and placebo-controlled design. Local tenderness and stimulus-response functions, mechanical pain thresholds (PPDT) in the temporal region and on the finger, and total tenderness score (TTS) were recorded. A local, prolonged, and mild to moderate tenderness was reported both in patients (P = 0.001) and in controls (P = 0.001) after the combination compared with the placebo. The response to the combination tended to be increased in patients. The stimulus-response function was leftward shifted after the combination, compared with baseline in both groups. No changes in PPDT or TTS were found after the infusions, whereas baseline PPDTs were decreased in ETTH compared with controls (PPDTfinger: P = 0.033; PPDTtemporal: P = 0.015). Intramuscular infusion of a combination of endogenous substances induced prolonged tenderness in both patients with episodic TTH and healthy subjects. The present results suggest an increased excitability of peripheral muscle afferents in TTH.

[The effect of serotonin on the healing of an experimental stomach ulcer following vagotomy]. / Vplyv serotoninu na zahoiuvannia eksperymental'noï vyrazky shlunka za umov vahotomiï.

On the model of gastric ulcer induced by stress with subsequent trunk vagotomy in rats it is shown that exogenic serotonin induces increased concentrations of serotonin in the gastric tissues, among them in the region of ulcer's defect, decreased amounts of histamine and increased serotonin-histamine indexes, and also promotes calming down of inflammatory phenomena and optimization of reparative processes in the region of ulcer.

A mouse model of focal cerebral ischemia for screening neuroprotective drug effects.

The aim of the present study was to investigate if the infarct area on the brain surface after middle cerebral artery (MCA) occlusion in the mouse is representative for the infarct volume and if this determination of brain injury can be used for screening neuroprotective drug effects. Cerebral infarction was induced by coagulating electrically the stem of the left MCA. After 48 hr, the brains were perfused with carbon black and the unstained infarct area was determined by means of an image analyzing system. The infarct volume was determined by calculating the infarct area on coronal slices and the distance between succeeding slices. The correlation between the area and the volume of infarction was significant (r = 0.81; p less than 0.001). N-methyl-D-aspartate (NMDA) antagonists, calcium antagonists, 5-hydroxytryptamine-1A (5-HT-1A) agonists, radical scavengers, and various drugs were investigated in the mouse model of MCA occlusion. Drugs were usually applicated before ischemia. The drugs that were found to be neuroprotective in the mouse model revealed similar effects in rat models of focal or global cerebral ischemia. These findings show that the presented mouse model with its simple technique of measuring the infarct size is suitable for screening purposes.