MDMA ('Ecstasy') enhances 5-HT1A receptor density and 8-OH-DPAT-induced hypothermia: blockade by drugs preventing 5-hydroxytryptamine depletion

One week after a single administration of 3,4-methylenedioxymethamphetamine (MDMA HCI, 30 mg/kg i.p.), 5-HT1A receptor density was significantly increased by approximately 25-30% in the frontal cortex and hypothalamus of rats. The increased density correlated with the potentiation of the hypothermic response to the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 1 mg/kg s.c.). Hypothalamic 5-HT7 receptors, which also bind 8-OH-DPAT, were not changed, however, by MDMA. Fluoxetine (5 mg/kg s.c.), ketanserin (5 mg/kg s.c.) or haloperidol (2 mg/kg i.p.), given 15 min prior to MDMA, prevented the depletion of 5-hydroxytryptamine (5-HT) induced by MDMA and also blocked the effects of this neurotoxin on 5-HT1A receptor density and on 8-OH-DPAT-induced hypothermia. The protection afforded by drugs against 5-HT loss did not correlate, however, with the antagonism of the acute hyperthermic effect of MDMA. The present results indicate that drugs able to prevent or to attenuate MDMA-induced 5-HT loss also prevent the changes in 5-HT1A receptor density as well as the enhanced hypothermic response to the 5-HT1A receptor agonist 8-OH-DPAT in MDMA-treated rats.     

Endothelium-independent relaxant effect of 5-hydroxytryptamine (5-HT) on the isolated rabbit facial vein

PURPOSE: To identify nursing diagnoses and interventions applicable for post-acute-phase battered women. METHODS: Eight battered women were interviewed twice for 2 hours. Gordon's functional health patterns provided the framework for data collection. FINDINGS: Fifty-three nursing diagnoses and 52 nursing interventions were indicated in the data; 24 nursing diagnoses and 26 nursing interventions were present in all participants' data. CONCLUSIONS: With the use of comprehensive interventions, nurses can make a major contribution to society by enabling battered women to move to a more protected lifestyle.     

A potent 5-hydroxytryptamine receptor (5-HT2A) antagonist, DV-7028, delays arterial thrombosis development in rats

In our study, we demonstrated that DV-7028: (3-[2-[4-(4-fluorobenzoyl)piperidin-1-yl]ethyl]-6, 7,8,9-tetrahydro-2H-pyrido [1,2,-a]-1,3,5-triazine-2, 4(3H)-dione maleate)--a selective 5-HT2A receptor antagonist, inhibited thrombus formation in the arterial thrombosis model and was completely ineffective in the prevention of venous thrombosis in the rat. In washed platelets prelabelled with 3H-serotonin, DV-7028 inhibited, in a dose-dependent manner, the collagen-induced secretion of serotonin. However, the uptake of serotonin into platelets was not affected by this substance. Administration of DV-7028 also inhibited platelet aggregation in the whole blood and platelet-rich plasma (PRP) induced by collagen, and diminished serotonin-induced aggregation of rat platelets in the presence of a sensitizing but nonaggregating amount of ADP, whereas it did not modify aggregation in PRP when induced by ADP. DV-7028 caused a concentration-dependent, almost parallel shift to the right of the concentration-response to serotonin for its pressor effect in the rat perfused tail artery. The present data demonstrate that DV-7028 exhibits 5-HT2A receptor antagonistic properties in the rat cardiovascular system, exhibits antithrombotic effect in the model of arterial but not venous thrombosis in rats. These results constitute further evidence of the possible importance of serotonin as a mediator of platelet thrombosis in arteries. Moreover, they can provide a useful tool for the prevention of various thrombotic diseases.     

Novel 5-hydroxytryptamine (5-HT3) receptor antagonists. I. Synthesis and structure-activity relationships of conformationally restricted fused imidazole derivatives

We prepared a novel series of conformationally restricted fused imidazole derivatives 4b, 4c and 4d (possessing 4,5,6,7-tetrahydroimidazo[4,5-c] pyridine and substituted 4,5,6,7-tetrahydro-1H-benzimidazole for 4b, 5,6,7,8-tetrahydroimidazo[1,2-a]pyridine for 4c and 5,6,7,8-tetrahydroimidazo[1,5-a]pyridine for 4d as a basic amine part and (2-methoxyphenyl)aminocarbonyl group as an aromatic-carbonyl part). Their activities were then evaluated as an 5-hydroxytryptamine (5-HT3) receptor antagonist which may be useful for the treatment of irritable bowel syndrome (IBS) as well as for nausea and vomiting associated with cancer chemotherapy. The most potent compound was N-(2-methoxyphenyl)-4,5,6, 7-tetrahydro-1H-benzimidazole-5-carboxamide 14 in this series with an ID50 value of 0.32 microgram/kg on the von Bezold-Jarisch reflex in rats and an IC50 value of 0.43 microM on the isolated colonic contraction in guinea pig, approximately ten and two times more potent than ondansetron 1, respectively. The structure activity relationships (SAR) study suggested that the high potency of 14 may be attributed to the suitable position and direction of the N-C-N centroid in the conformationally restricted imidazole ring against the planar (2-methoxyphenyl)aminocarbonyl part in the binding of 14 to the receptor.     

Regional brain heating during microwave exposure (2.06 GHz), warm-water immersion, environmental heating and exercise

Nonuniform heating may result from microwave (MW) irradiation of tissues and is therefore important to investigate in terms of health and safety issues. Hypothalamic (Thyp), cortical (Tctx), tympanic (Tty), and rectal (Tre) temperatures were measured in rats exposed in the far field, k-polarization (i.e., head pointed toward the transmitter horn and E-field in vertical direction) to two power densities of 2.06 GHz irradiation. The high-power density (HPM) was 1700 mW/cm2 [specific absorption rate (SAR): hypothalamus 1224 W/kg; cortex 493 W/kg]; the low-power density (LPM) was 170 mW/cm2 (SAR: hypothalamus 122.4 W/kg; cortex 49.3 W/kg). The increase (rate-of-rise, in degrees C/s) in Thyp was significantly greater than those in Tctx or Tre when rats were exposed to HPM. LPM produced more homogeneous heating. Quantitatively similar results were observed whether rats were implanted with probes in two brain sites or a single probe in one or the other of the two sites. The qualitative difference between regional brain heating was maintained during unrestrained exposure to HPM in the h-polarization (i.e., body parallel to magnetic field). To compare the temperature changes during MW irradiation with those produced by other modalities of heating, rats were immersed in warm water (44 degrees C, WWI); exposed to a warm ambient environment (50 degrees C, WSED); or exercised on a treadmill (17 m/min 8% grade) in a warm ambient environment (35 degrees C, WEX). WWI produced uniform heating in the regions measured. Similar rates-of-rise occurred among regions following WSED or WEX, thus maintaining the pre-existing gradient between Thyp and Tctx These data indicate that HPM produced a 2-2.5-fold difference in the rate-of-heating within brain regions that were separated by only a few millimeters. In contrast, more homogeneous heating was recorded during LPM or nonmicrowave modalities of heating.     

Differential distribution of [3H]sumatriptan binding sites (5-HT1B, 5-HT1D and 5-HT1F receptors) in human brain: focus on brainstem and spinal cord

We report on the autoradiographic distribution of 5-HT1B, 5-HT1D and 5-HT1F receptor subtypes in human brain, focusing on the brainstem and cervical spinal cord. We have used [3H]sumatriptan as a radioligand in the presence of suitable concentrations of 5-CT (5-carboxamidotryptamine) to define 5-HT1F receptors, and ketanserin, to discriminate between 5-HT1B and 5-HT1D receptors. In the brainstem the highest concentrations of [3H]sumatriptan binding sites were seen in substantia nigra. The spinal trigeminal nucleus, substantia gelatinosa of the spinal cord, nucleus of the tractus solitarius and periaqueductal grey, also showed significant levels of [3H]sumatriptan binding sites. In the brainstem and spinal cord the total population of 5-CT-insensitive receptors, corresponding to 5-HT1F receptors, ranged from 9.8% in the periaqueductal grey to 53.4% in the substantia gelatinosa. This population represented 67.0% of binding in layer V of the frontal cortex. The decrease in [3H]sumatriptan binding in the presence of 200 nM ketanserin, indicative of the presence of 5-HT1D receptors, was very limited throughout the human brain, only reaching 20% of total specific binding over the periaqueductal grey. The proportion of [3H]sumatriptan binding sites displaced by 5-CT and insensitive to ketanserin, corresponding to 5-HT1B receptors, was, in general, the most abundant, ranging from 43.8% in substantia gelatinosa to 69.9% in the periaqueductal grey. Significant levels of 5-HT1B and 5-HT1D receptors found in migraine control pain areas suggest their involvement in antinociceptive mechanisms.     

Synthesis of the selective 5-hydroxytryptamine 4 (5-HT4) receptor agonist (+)-(S)-2-chloro-5-methoxy-4-[5-(2-piperidylmethyl)-1,2,4-oxadiazol-3-y l]aniline

A 52-year-old white woman was first diagnosed with a tumor of the right optic nerve in 1972. She remained asymptomatic until 1992, when she had a seizure on the left side of her body from a frontoparietal glioblastoma multiforme. Ophthalmic examination revealed enlargement of the eye tumor. This case provides clinical documentation spanning 20 years of a growing, pigmented tumor of the optic nerve head shown histopathologically to be a retinal pigment epithelial adenoma.     

Effects of mesulergine treatment on diet selection, brain serotonin (5-HT) and dopamine (DA) turnover in free feeding rats

1. The effects of mesulergine, a 5-hydroxytryptamine (5-HT) receptor antagonist with dopamine (DA) agonistic properties, on rats diet selection over a seven day period and on 5-HT and DA turnover was studied. 2. Three groups of male Wistar rats were individually caged and ad libitum fed with a standard (SD) and 50% sweet carbohydrate enriched diet (CED). Food intake was measured daily 4 hrs and 24 hrs after i.p. injections of mesulergine (1 and 3 mg/kg) or vehicle. 5-HT and 5-HIAA in hypothalamus (Hy), Striatum (St) and hippocampus (Hi) as well as DA and DOPAC in (Hy) and (St) were assayed at the 8th day of the experiment. 3. There was a dose dependent increase of SD consumption 4 hrs after mesulergine treatment while the CED remained unchanged with total food intake dose dependently increased as a consequence. At 24 hrs measurements SD consumption was increased only for the dose of 1 mg/kg of mesulergine, while a dose dependent decrease of CED intake was observed. Total food intake was unchanged for the dose of 1 mg/kg and decreased with the dose of 3 mg/kg consequently. A dose dependent decrease of rats body weight was observed too. 4. A significant increase of 5-HIAA/5-HT ratio in (Hy) and (St) for the dose of 1 mg/kg and in (Hi) for the dose of 3 mg/kg with no changes of DA turnover were found. 5. The above data suggest a dual mode of action of mesulergine presented as a short term hyperphagia due to simultaneous antiserotonergic and dopaminergic activity and long-term hypophagia due to long-term agonistic effects of dopaminergic neurons.     

Increase of 5-HT7 (serotonin-7) and 5-HT1A (serotonin-1A) receptor mRNA expression in rat hippocampus after adrenalectomy

Kinematic and electromyographic (EMG) analysis of a target-directed, maximal velocity movement was used to investigate the effects of high-force eccentric exercise on the neuromuscular control of elbow flexion. Ten non-weight-trained females [19.6 (1.6) years old] performed 50 maximal velocity elbow flexion movements from 0 to 1.58 rad (90 degrees), as rapidly as possible in response to a light stimulus, while kinematic and triphasic EMG parameters were measured. This was done three times pre-exercise, immediately and 1, 2, 3, 4, and 5 days following the 50 maximal eccentric elbow flexion actions. The eccentric exercise caused lengthening of kinematic parameters including total movement time and time to peak velocity. The EMG elements of the biceps brachii (b.) motor time, time to peak EMG, biceps b. burst duration, and the latency period between biceps b. and triceps b. bursts were lengthened post-exercise. These changes persisted for up to 5 days post-exercise. The exercise also caused a large increase in serum creatine kinase (CK) activity. It was concluded that high-force eccentric exercise in this population caused prolonged changes in neuromuscular control that were a function of exercise-induced disruption of the skeletal muscle. Compensation in the central motor program was such that the components of the triphasic EMG pattern were systematically lengthened.     

Differential effects of serotonin (5-HT) lesions and synthesis blockade on neuropeptide-Y immunoreactivity and 5-HT1A, 5-HT1B/1D and 5-HT2A/2C receptor binding sites in the rat cerebral cortex

The present study was aimed at comparing the effects of serotonin (5-HT) synthesis blockade using chronic administration of p-chlorophenylalanine (PCPA) and 5,7-dihydroxytryptamine injections of variable volume (3 vs. 6 microl) on the density of NPY immunoreactive (Ir) neurons and binding of [3H]8-OH-DPAT, S-CM-G[125I]TNH2 and [125I]DOI to 5-HT1A, 5-HT1B/1D, and 5-HT2A/2C receptors in rat cortical regions. Three weeks after large but partial (89% depletion in 5-HT tissue concentration) lesions of 5-HT neurons no changes in neither NPY immunoreactivity nor 5-HT receptor binding were detected. The complete 5,7-DHT lesions produced increases in the number of NPY-Ir neurons in the upper regions of the cingular (134%), frontal (140%) and parietal cortex (48%) and corresponding decreases in 5-HT2A/2C binding (16-26%). No changes in 5-HT1A and 5-HT1B/1D binding were observed after lesions of this kind. After PCPA treatment, decreases in NPY-Ir neurons density (22-40%) and increases in 5-HT1A and 5-HT1B/1D receptor binding sites (20-50%) were distributed in both upper and deeper cortical regions. The lack of effect of the partial lesion suggests that spared 5-HT neurons may exert compensatory mechanisms up to a large extent. The changes in NPY immunoreactivity and 5-HT2A/2C binding detected in the upper regions of the cortex after complete 5-HT lesions probably result from local cellular rearrangements, whereas blocking 5-HT synthesis has more widespread influence on NPY neurons and on 5-HT1A and 5-HT1B/1D receptor subtypes. Moreover, decreases in DOPAC concentrations detected only after complete lesions suggest that the involvement of catecholaminergic transmission may also differentiate 5,7-DHT and PCPA treatments. Altogether, these data suggest that different receptor subtypes might be involved in 5-HT-NPY relationships.     

Pharmacokinetics and CNS pharmacodynamics of the 5-HT1A agonist buspirone in humans following acute L-tryptophan depletion challenge

This study was designed to evaluate the relationship between the pharmacokinetic(s) (PK) and CNS pharmacodynamic(s) (PD) of buspirone, an antidepressant/anxiolytic, in 6 healthy male volunteers placed on an acute L-tryptophan deficient (ATD) diet. The study was a randomized, double-blind, placebo-controlled, four-period, three-way crossover study. The first study period was a single-blind familiarization period in which all subjects received placebo. During the remaining three study periods, subjects received either placebo, 10 mg or 30 mg oral buspirone. Subjects were administered the ATD diets 5 h prior to buspirone/placebo administration during each study period. All subjects underwent serial measurements of resting electroencephalography (REEG) and vigilance electroence-phalography (VEEG), cognitive tests, subjective rating scales, and blood was sampled for determination of unbound plasma L-tryptophan, serum prolactin, serum cortisol and plasma buspirone and its active metabolite, 1-pyrimdylpiperazine (1-PP). The ATD diet reduced the unbound plasma L-tryptophan concentrations to 20% of their baseline values. The intraindividual and interindividual variability in the unbound L-tryptophan concentration drop was less than 10% and 15%, respectively. Peak L-tryptophan depletion occurred 5 h after ATD diet was administered; L-tryptophan depletion lasted for approximately 11 h, and L-tryptophan concentrations recovered to baseline values approximately 13 h after administration of the ATD diet. PK-PD analysis for buspirone showed that: 1) peak plasma concentration (Cmax) and total area under the plasma concentration-time curve (AUC infinity) for buspirone following the 10 mg dose in this study were higher than those reported previously in the literature; 2) there was a transient response in the neuroendocrine measures, subjective rating scales and the EEG, but no changes in the cognitive tests with increasing doses of buspirone; 3) the PD measures were correlated with the doses of buspirone, but not with plasma concentrations of buspirone and 1-PP; and 4) the subjective rating scales were the most sensitive indicators of buspirone's CNS effects. This study provides evidence that ATD diet is a simple, specific and non-toxic experimental method to lower plasma L-tryptophan concentrations and thereby (indirectly) deplete brain tryptophan and serotonin (5-HT) concentrations. The ATD challenge may serve as a model of depression in healthy volunteers because of its ability to induce transient symptoms of the disease. Comparison of the results from this study to those reported in the literature suggests that the use of the ATD diet decreases the buspirone-induced neuroendocrine response, increases the buspirone-induced changes in subjective rating scales and, at the same time, increases the systemic exposure to buspirone and 1-PP.     

Endothelial expression of the 5-hydroxytryptamine1B antimigraine drug receptor in rat and human brain microvessels

In addition to triggering vasoconstriction of peripheral blood vessels, which led to its discovery as a circulating neurohormone 50 years ago, serotonin (5-hydroxytryptamine) acts as a neurotransmitter/ modulator in the central nervous system and regulates local cerebral blood flow and vascular permeability through direct and indirect effects on intraparenchymal microvessels. Among the various 5-hydroxytryptamine receptors which mediate these effects, particular attention has been paid to the 5-hydroxytryptamine1B and 5-hydroxytryptamine1D subtypes, as the preferred targets of modern antimigraine agents. Immunoelectron microscopic labeling of the 5-hydroxytryptamine1B receptor in rat brain parenchyma has revealed a distinct localization to the endothelium of microvessels, which was predominantly cytoplasmic as opposed to membrane-bound, contrary to that on preterminal unmyelinated axons [Riad et al. (1997) Soc. Neurosci. Abstr. 23, 1214]. Similar observations have now been made in human cortical tissue, in which the expected localization of the vascular 5-hydroxytryptamine1B receptor to periarteriolar myocytes was also confirmed. Such a dual localization in human brain microvessels suggests that the 5-hydroxytryptamine1B receptor might mediate opposite effects, vasodilatory and contractile, depending upon its activation by circulating or centrally released 5-hydroxytryptamine. It raises new possibilities as regards 5-hydroxytryptamine effects on human brain microvessels in health and disease, and notably the triggering of migraine headache.     

The 5-HT1A and 5-HT2A/2C receptor antagonists WAY-100635 and ritanserin do not attenuate D-fenfluramine-induced fos expression in the brain

In a prospective randomised study we investigated end-tidal carbon dioxide levels during standard versus active compression-decompression (ACD) cardiopulmonary resuscitation (CPR) assuming that the end-tital carbon dioxide reflects cardiac output during resuscitation. In each group 60 patients with out-of-hospital cardiac arrest were treated either with the standard or the ACD method. End-tidal CO2 (p(et)CO2, mmHg) was assessed with a side-stream capnometer following intubation and then every 2 min up to 10 min or restoration of spontaneous circulation (ROSC). There was no difference in p(et)CO2 between both patient groups. However, CO2 was significantly higher in patients who were admitted to hospital as compared to patients declared dead at the scene. All of the admitted patients had a p(et)CO2 of at least 15 mmHg no later than 2 min following intubation, none of the dead patients ever exceeded 15.5 mmHg. From these data we conclude that capnometry adds valuable information to the estimation of a patient's prognosis in the field (threshold, 15 mmHg), but we could not detect any difference in p(et)CO2 between ACD and standard CPR.     

The relationship between the degree of neurodegeneration of rat brain 5-HT nerve terminals and the dose and frequency of administration of MDMA ('ecstasy')

The effect of varying the dose and frequency of administration of 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') on both the acute hyperthermic response and the long term neurodegeneration of 5-hydroxytryptamine (5-HT) nerve terminals in the brain has been studied in Dark Agouti rats. A single injection (4-15 mg/kg i.p.) of MDMA produced immediate dose-related hyperthermia and a dose-related decrease in 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and [3H]paroxetine binding in regions of the brain 7 days later, with a dose of 4 mg/kg having no degenerative effect. This dose was also without effect when given once daily for 4 days, but produced a marked loss of [3H]paroxetine binding and indole concentration ( approximately 55%) when given twice daily for 4 days. When a dose of 4 mg/kg was given twice weekly for 8 weeks it had no effect on these serotoninergic markers, despite a clear anorectic effect of the drug being seen. These data demonstrate that MDMA-induced neurodegeneration is related to both the dose and frequency of administration and indicate that damage to 5-HT neurones can occur in the absence of a hyperthermic response to the drug. We suggest that damage occurs when endogenous free radical scavenging mechanisms become overwhelmed or exhausted.     

Effects of galanin on 8-OH-DPAT induced decrease in body temperature and brain 5-hydroxytryptamine metabolism in the mouse

The objective of this study was to describe the health care utilization and prospective predictors of high-cost primary-care back pain patients. In the primary-care clinics of a large, staff model health maintenance organization in western Washington State, 1059 subjects were selected from consecutive patients presenting for back pain. The design was a 1-year prospective cohort study. Patients' were interviewed 1 month after an index primary-care back pain visit. Costs (back pain and total) and utilization (back pain primary-care follow-up visits, back pain specialty visits, back pain hospitalizations, back pain radiologic procedures, and pain medicine fills) were tracked over the next 11 months. Predictors assessed at 1 month were back pain diagnosis (disc disorder/sciatica, arthritis, vs. other), chronic pain grade (measure of pain intensity and related dysfunction), pain persistence (days with pain in prior 6 months), depressive symptomatology, and back pain-related disability compensation (ever/never). For the sample, 21% of patients with back pain costs > or = $600 (high back pain costs) accounted for 66% of back pain costs, 42% of total costs, 55% of primary-care follow-up visits for back pain, 91% of back pain specialty visits, 100% of back pain hospitalizations, 51% of back pain radiologic procedures, and 52% of pain medicine fills. The 21% with total costs > or = $2700 (high total costs) accounted for 67.7% of total costs, 52% of back pain costs, 29% of primary-care follow-up visits for back pain, 66% of back pain specialty visits, 100% of back pain hospitalizations, 39% of back pain radiologic procedures, and 42% of pain medicine fills. Multivariable logistic regression analyses indicated that increasing chronic pain grade, more persistent pain, and disc disorder/sciatica were strong independent predictors of high total and high back pain costs. Increasing depressive symptoms significantly predicted high total but not high back pain costs. Back pain disability compensation predicted high back pain but not high total costs. A minority of primary-care back pain patients accounted for a majority of health-care costs. Patients with high back pain costs accounted for more back pain-related health-care utilization than did patients with high total costs. Factors predicting subsequent high costs suggest behavioral interventions targeting dysfunction, pain persistence, and depression may reduce health-care utilization and prevent accumulation of high health-care costs among primary-care back pain patients.     

Long-term effects of portacaval anastomosis on the 5-hydroxytryptamine, histamine, and catecholamine neurotransmitter systems in rat brain

Portacaval anastomosis (PCA) in the rat is used as a model for portal systemic encephalopathy. Changes in the serotonergic, histaminergic, and catecholaminergic neurotransmitter systems are often found shortly after PCA. We have examined the long-term effects of PCA on the aminergic systems in brains of male Wistar rats, which 8 months previously had been subjected to PCA. Precursors, amines, and metabolites were assayed by HPLC. Eight months after PCA, the catecholamine levels were unchanged in all brain regions. In contrast, tryptophan was evenly increased throughout the brain. The accumulation of 5-hydroxytryptophan after decarboxylase inhibition (NSD-1015; 100 mg/kg i.p.) and the endogenous levels of 5-hydroxyindoleacetic acid were significantly higher in PCA rats, particularly in the hypothalamus and midbrain, whereas 5-hydroxytryptamine concentrations were unchanged. Histamine levels were elevated throughout the brain with the greatest increase found in the hypothalamus and in the striatum. tele-Methylhistamine levels were significantly elevated in cortex and hypothalamus. We conclude that 8 months after PCA, catecholaminergic systems had reestablished their homeostasis, whereas serotonergic and histaminergic systems still show profound disturbances in their function. With histamine, this is reflected as an increase in the amounts of both transmitter and metabolite; serotonergic neurons respond by increasing only the level of the metabolite.     

Immunohistochemical localisation of the serotonin 5-HT2B receptor in mouse gut, cardiovascular system, and brain

We recently reported the cloning of a new member of the serotonin 5-HT2 family, the 5-HT2B receptor. We now report the production and characterisation of a specific antiserum directed against the C-terminal portion of the mouse 5-HT2B receptor. After affinity purification, this polyclonal antibody recognises specifically the mouse 5-HT2B receptor. Immunohistochemical analysis of cryosections from various adult mouse tissues reveals a major 5-HT2B receptor expression in stomach, intestine and pulmonary smooth muscles as well as in myocardium. Furthermore, the antiserum recognises specific areas of the mouse brain, including cerebellar Purkinje cells and their projection areas.