Effects Of Atropine Research Articles

Automated high-throughput measurement of body movements and cardiac activity of Xenopus tropicalis tadpoles

Xenopus tadpoles are an emerging model for developmental, genetic and behavioral studies. A small size, optical accessibility of most of their organs, together with a close genetic and structural relationship to humans make them a convenient experimental model. However, there is only a limited toolset available to measure behavior and organ function of these animals at medium or high-throughput. Herein, we describe an imaging-based platform to quantify body and autonomic movements of Xenopus tropicalis tadpoles of advanced developmental stages. Animals alternate periods of quiescence and locomotor movements and display buccal pumping for oxygen uptake from water and rhythmic cardiac movements. We imaged up to 24 animals in parallel and automatically tracked and quantified their movements by using image analysis software. Animal trajectories, moved distances, activity time, buccal pumping rates and heart beat rates were calculated and used to characterize the effects of test compounds. We evaluated the effects of propranolol and atropine, observing a dose-dependent bradycardia and tachycardia, respectively. This imaging and analysis platform is a simple, cost-effective high-throughput in vivo assay system for genetic, toxicological or pharmacological characterizations.

Influence of muscarinic receptor modulators on interacerebroventricular injection of arachydonylcyclopropylamide induced antinociception in mice

The interaction between antinociception induced by CB1 agonist and muscarinic receptor modulators has not been studied yet. In the present study, the effect of pilocarpine (a muscarinic agonist) and atropine (a muscarinic antagonist) on arachidonylcyclopropylamide (ACPA, a CB1 agonist) induced antinociception was studied in mice. In this study the antinociceptive effect of intracerebroventricular administration of ACPA (0.001–2μg/mice) or intraperitoneal injection of pilocarpine (2.5–20mg/kg) or atropine (1 and 5mg/kg) were studied individually. Then the effect of co-administration of pilocarine (2.5mg/kg) or atropine (5mg/kg) and ACPA (0.001–2μg/mice) were studied as well. ACPA and pilocarpine induced antinociception in mice but atropine did not. Pilocarpine potentiated but atropine antagonized the antinociceptive effect of ACPA. It is concluded that ACPA induced antinociception is influenced by muscarinic receptor modulators in mice.

Involvement of GABA transporters in atropine-treated myopic retina as revealed by iTRAQ quantitative proteomics.

Atropine, a muscarinic antagonist, is known to inhibit myopia progression in several animal models and humans. However, the mode of action is not established yet. In this study, we compared quantitative iTRAQ proteomic analysis in the retinas collected from control and lens-induced myopic (LIM) mouse eyes treated with atropine. The myopic group received a (−15D) spectacle lens over the right eye on postnatal day 10 with or without atropine eye drops starting on postnatal day 24. Axial length was measured by optical low coherence interferometry (OLCI), AC-Master, and refraction was measured by automated infrared photorefractor at postnatal 24, 38, and 52 days. Retinal tissue samples were pooled from six eyes for each group. The experiments were repeated twice, and technical replicates were also performed for liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis. MetaCore was used to perform protein profiling for pathway analysis. We identified a total of 3882 unique proteins with <1% FDR by analyzing the samples in replicates for two independent experiments. This is the largest number of mouse retina proteome reported to date. Thirty proteins were found to be up-regulated (ratio for myopia/control > global mean ratio + 1 standard deviation), and 28 proteins were down-regulated (ratio for myopia/control < global mean ratio - 1 standard deviation) in myopic eyes as compared with control retinas. Pathway analysis using MetaCore revealed regulation of γ-aminobutyric acid (GABA) levels in the myopic eyes. Detailed analysis of the quantitative proteomics data showed that the levels of GABA transporter 1 (GAT-1) were elevated in myopic retina and significantly reduced after atropine treatment. These results were further validated with immunohistochemistry and Western blot analysis. In conclusion, this study provides a comprehensive quantitative proteomic analysis of atropine-treated mouse retina and suggests the involvement of GABAergic signaling in the antimyopic effects of atropine in mouse eyes. The GABAergic transmission in the neural retina plays a pivotal role in the maintenance of axial eye growth in mammals.

The heart cannot pump blood that it does not receive.

The heart cannot pump blood that it does not receive.

Reactions of methylphosphonic difluoride with human acetylcholinesterase and oximes – Possible therapeutic implications

Highly toxic organophosphorus (OP) nerve agents are well characterized regarding chemical, biological and toxicological properties and the effectiveness of standard atropine and oxime therapy. Open literature data on the key nerve agent precursor methylphosphonic difluoride (DF) are scarce. To fill this gap the reactions of DF and its main degradation product methylphosphonofluoridic acid (MF) with human acetylcholinesterase (AChE) and the oximes obidoxime, HI-6 and 2-PAM were investigated in vitro. DF and MF were found to be weak inhibitors of human AChE being at least five orders less potent compared to the nerve agent sarin. Incubation of human AChE with millimolar DF and MF and subsequent addition of obidoxime and HI-6 resulted in a concentration-dependent decrease of AChE activity. This effect was not observed when incubating highly diluted AChE with oximes. The most likely explanation for this phenomenon is an inhibitory effect of phosphonyloximes formed by direct reaction of DF or MF with obidoxime and HI-6. These data indicate that high DF doses, resulting in millimolar blood and tissue DF/MF concentrations, are necessary to induce cholinergic signs and that under these conditions treatment with obidoxime and HI-6 may even worsen the poisoning.

Topical Ophthalmic Atropine in Horses – An Experimental Study

Reasons for performing studyTopical administration of atropine is an important part of the treatment of equine uveitis. However, very high doses of topically administered atropine have been associated with decreased gut motility and colic in horses.ObjectivesTo evaluate systemic effects of topical atropine in doses used clinically in horses, with emphasis on gut motility and ability to induce colic.Study designRandomised, blinded, controlled crossover study.MethodsFour horses received placebo eye drops (saline) and 2 different protocols of topical atropine administration during 120 h with 35 days washout periods in between different treatments. One drop of 1% atropine solution was administered unilaterally at 3‐h intervals for 48 h and at 12‐h intervals for another 72 h (high dose), whereas the low dose group was given alternating treatment with atropine and saline according to the same protocol. In the placebo group, saline was administered at 3‐h intervals for 48 h and at 12‐h intervals for another 72 h. All horses were walked for 10 min 3 times a day. Pupillary light reflexes, heart rate, respiratory rate, gut sounds and clinical signs of abdominal pain were monitored every 3 h and faecal output once daily.ResultsNone of the horses showed any signs of abdominal pain. Gut sounds were present at every auscultation in all horses. Gut sound scores were significantly lower during the high dose regime (P = 0.0007) compared to placebo, but not during the low dose regime (P = 0.17).ConclusionsTopically administered atropine in clinically relevant doses temporarily reduced gut motility, but did not cause ileus or colic in healthy horses receiving a small amount of daily exercise. However, this effect may be additive to other factors that reduce gut motility in horses with uveitis, such as pain and stress in relation to hospitalisation.Ethical animal research: The regional Ethical Committee (Uppsala Djurförsöksetiska nämnd, Sweden, Dnr C372/12) approved the use of the horses in this study. Sources of funding: None. Competing interests: None.

A randomized trial of adding a plano lens to atropine for treatment of residual amblyopia

Atropine is an effective treatment for amblyopia due to strabismus and/or anisometropia.1-3 Nevertheless, some patients have residual amblyopia following atropine treatment.2-3 We conducted a randomized clinical trial to evaluate the effectiveness of augmenting the effect of atropine by changing the spectacle lens over the fellow eye to plano in children with residual amblyopia.

Physiological and Ethological Effects of Caffeine, Theophylline, Cocaine and Atropine; Study Using the Ant Myrmica sabuleti (Hymenoptera, Formicidae) as A Biological Model

Aiming to check if ants can be used as biological models, we studied the effects of four alkaloids on the ant Myrmica sabuleti. Caffeine and theophylline increased the ants’ linear speed, decreased their precision of reaction and their food consumption, did not affect their response to pheromones, nor their audacity, largely increased their conditioning ability and their memory; ants did not become habituated to nor dependent on these alkaloids. The effects of caffeine exponentially decreased in the course of time; those of theophylline slowly decreased sigmoidally after a latency period. Cocaine decreased the ants’ linear speed, their precision of reaction, their response to pheromones and their consumption of food; it increased their audacity; under its consumption, ants became unable to acquire conditioning. Ants became habituated to and dependent on such an alkaloid. The effects of cocaine rapidly vanished in the course of time. Atropine did not affect the ants’ locomotion, decreased their precision of reaction and their response to pheromones because it reduced their olfactory perception; it did not affect their audacity, decreased their food consumption, increased the speed in acquiring conditioning but not the quality of the resulting conditioning; it slightly increased their memory. Ants did not become habituated to, nor dependent on this alkaloid. The effects of atropine vanished in about 20 hrs - 30 hrs. These effects are in agreement with those known by physiologists, psychologists and doctors in medicine; observations made on ants even lead to more precise deductions. Consequently, ants can efficiently be used as biological models.

Dose dependent effects of intramuscular administered atropine on heart rate in Trachemys scripta (879.16)

Atropine sulfate is a common anticholingeric drug that is used in human medicine and veterinary medicine, as well as in scientific research. At doses less than 0.1mg/kg, it is used to treat bradycardia, ptyalism, and as an antidote for organophosphate poisoning. Although the effects of atropine have not been thoroughly examined in reptiles, previous studies utilized atropine, 1‐5mg/kg doses, to abolish shunting in reptiles, including snakes, crocodilians, and chelonians . In the present study, we investigated the influence of intramuscular administered atropine on heart rate in freshwater turtles, Trachemys scripta. To achieve this objective, an untethered electrocardiogram device recorded continuously in healthy female adult turtles (n=5, m=1‐2kg) before, during, and after the injections of veterinary grade atropine (0.01‐5mg/kg I.M.) with minimal observer interference. Heart rate was then derived from these measurements. Turtles showed a rapid increase to the peak heart rate less than ten minutes after the injection of atropine, except after the 0.01mg/kg dose, then gradually returned to the resting heart rate. In all doses above 0.01mg/kg, the length of the peak elevated heart rate constitutes about 1/5 of the total time atropine has an effect on heart rate. As a result, the extent of the elevated heart rates in the turtles increased exponentially as the dose of atropine also increased. Thus, we conclude that the lasting consequence of atropine on elevated heart rate is dose‐related. These results suggest that scientists can effectively eliminate shunting in turtles at lower atropine doses without subjecting the animal to prolonged tachycardia and associated cardiovascular adjustments.Grant Funding Source: Supported by NSF (1121324‐IOS)

Acute Adult Onset Comitant Esotropia Associated with Accommodative Spasm

Acute onset comitant esotropia associated with spasm of accommodation in children and adults is a rare clinical condition. When occurring with pupillary miosis and restricted ocular motility, it is referred to as "spasm of near reflex" (SNR) and may require neurological investigation. The natural history of SNR depends on its etiology. There is little information in the literature regarding the long-term follow-up of SNR and the stability of visual signs and symptoms following cessation of treatment. We report a case of SNR in an otherwise healthy young male, and discuss the presentation, clinical investigations, management, response to treatment, and 1-year follow-up. A 23-year-old male patient reported to the clinic with sudden onset of blurred vision, inward deviation of the eyes, and binocular diplopia. On examination, he was diagnosed to have acute onset esotropia resulting from SNR. He was treated with cycloplegic medications and vision therapy. The condition resolved following 1 year and there has been no recurrence. Acute adult onset esotropia occurring with accommodative spasm responds favorably to cycloplegic medications but may need a longer course of treatment for successful resolution and stability.

Pulmonary effects of intravenous atropine induce ventilation perfusion mismatch.

Atropine is used for a number of medical conditions, predominantly for its cardiovascular effects. Cholinergic nerves that innervate pulmonary smooth muscle, glands, and vasculature may be affected by anticholinergic medications. We hypothesized that atropine causes alterations in pulmonary gas exchange. We conducted a prospective interventional study with detailed physiologic recordings in anesthetized, spontaneously breathing rats (n = 8). Animals breathing a normoxic gas mixture titrated to a partial arterial pressure of oxygen of 110-120 were exposed to an escalating dose of intravenous atropine (0.001, 0.01, 0.1, 5.0, and 20.0 mg/kg body mass). Arterial blood gas measurements were recorded every 2 min (×5) at baseline, and following each of the 5 doses of atropine. In addition, the animals regional pulmonary blood flow was measured using neutron-activated microspheres. Oxygenation decreased immediately following intravenous administration of atropine, despite a small increase in the volume of inspired air with no change in respiratory rate. Arterial blood gas analysis showed an increase in pulmonary dysfunction, characterized by a widening of the alveolar-arteriole gradient (p < 0.003 all groups except for the lowest dose of atropine). The microsphere data demonstrates an abrupt and marked heterogeneity of pulmonary blood flow following atropine treatment. In conclusion, atropine was found to decrease pulmonary gas exchange in a dose-dependent fashion in this rat model.

The effect of low-concentration atropine combined with auricular acupoint stimulation in myopia control

To compare the effect of myopia control between patients treated with low-concentration atropine eye drops combined with auricular acupoint stimulation and those treated with atropine alone. Single-blinded randomized controlled clinical trial in a regional teaching hospital. The patients received either topical 0.125% atropine nightly plus auricular acupoint stimulation (0.125A + ACU group) or topical 0.125% atropine alone nightly (0.125A group). The changes in spherical equivalent (SE), axial length (AL), anterior chamber depth (ACD), and intraocular pressure (IOP) per year were compared between the two groups. Seventy-three of 110 total patients (66.4%) completed at least 6 months of follow-up. Patients in the 0.125A + ACU group had less myopic progression and AL elongation (-0.41 diopter and 0.24 mm/year) than those in the 0.125A group (-0.66 diopter and 0.32 mm/year) (mean follow-up 14.7 months, p < 0.0001 and p = 0.02, respectively). The ACD increased more in the 0.125A + ACU group than in the 0.125A group (0.076 mm vs. 0.023 mm/year, p = 0.0004). IOP decreased more in the 0.125A + ACU group than in the 0.125A group (-1.01 mmHg vs. -0.13 mmHg/year, p = 0.007). A decrease of 1 mmHg of IOP correlated with a decrease of myopic progression of 0.021 diopter/year (p = 0.006). Patients treated with 0.125% atropine eye drops plus auricular acupoint stimulation had less myopic progression, less axial length elongation, more anterior chamber deepening, and greater IOP reductions than those treated with 0.125% atropine alone. Auricular acupoint stimulation in combination with low-concentration topical atropine was beneficial for myopia control.

Atropine Slows Myopia Progression More in Asian than White Children by Meta-analysis

To conduct a meta-analysis on the effects of atropine in slowing myopia progression and to compare Asian and white children and randomized controlled trials (RCTs) and observational studies. Randomized controlled trials and observational studies that assessed the effects of all concentrations of atropine in slowing myopia progression in children were searched from MEDLINE, EMBASE, and the Cochrane Library up to April 2013. Jadad scoring was used to evaluate the quality of RCTs, and the Newcastle-Ottawa Scale was used for observational studies. Four RCTs and seven cohort studies (a kind of observational study) with 1815 children aged 5 to 15 years were included. The children had a baseline refraction of -0.50 to -9.75 diopters (D) and were followed up for 22.0 months (range, 12.0 to 36.5 months). The weighted mean differences in myopia progression in RCTs and cohort studies of Asian children were 0.55 D per year (p < 0.01) and 0.54 D per year (p < 0.001), respectively, and 0.35 D per year (p = 0.01) in cohort studies of white children. Compared with placebo, the risk of fast myopia progression (>1.0 D per year) using atropine was significantly decreased in both RCTs (odds ratio [OR], 0.14; p < 0.01) and cohort studies (OR, 0.08; p < 0.01), and the benefit of slow myopia progression (<0.50 D per year) using atropine was significantly increased in both RCTs (OR, 6.73; p < 0.01) and cohort studies (OR, 22.10; p < 0.01). Atropine could significantly slow myopia progression in children, with greater effects in Asian than in white children. Randomized controlled trials and cohort studies provided comparable effects.

N‐butylscopolammonium bromide causes fewer side effects than atropine when assessing bronchoconstriction reversibility in horses with heaves

Bronchospasm results in airway obstruction in horses with heaves. Atropine is the most potent bronchodilator drug currently available for horses, but is associated with side effects that limit its use. Like atropine, N-butylscopolammonium bromide (NBB) is an anticholinergic agent with bronchodilatory properties. To compare the bronchodilating effects and side effects of atropine and NBB in horses with heaves. Cross-over experiment using horses with heaves. Eight horses with heaves were administered atropine and NBB, using a cross-over design. Heart rate, pupillary dilatation, transrectal palpation, lung mechanics (maximal changes in transpulmonary pressure, pulmonary resistance and elastance) and arterial blood gases were assessed before and 10 and 30 min after drug administration. One horse treated with atropine developed colic. Significant pupillary dilatation was observed only with atropine. Tachycardia developed in all horses, but was more marked with atropine. Lung function improved with both drugs, but elastance values had returned to baseline at 30 min with NBB. There was no improvement in arterial hypoxaemia with either drug. The study indicated that the bronchodilatory properties of NBB were not statistically different from those of atropine, but were of shorter duration. N-butylscopolammonium bromide was associated with fewer systemic side effects, and therefore NBB should be preferred over atropine when assessing the reversibility of airway obstruction in horses.

In a non‐human primate model, aging disrupts the neural control of intestinal smooth muscle contractility in a region‐specific manner

BackgroundIncidences of gastrointestinal (GI) motility disorders increase with age. However, there is a paucity of knowledge about the aging mechanisms leading to GI dysmotility. Motility in the GI tract is a function of smooth muscle contractility, which is modulated in part by the enteric nervous system (ENS). Evidence suggests that aging impairs the ENS, thus we tested the hypothesis that senescence in the GI tract precipitates abnormalities in smooth muscle and neurally mediated contractility in a region-specific manner.MethodsJejunal and colonic circular muscle strips were isolated from young (4–10 years) and old (18+ years) baboons. Myogenic responses were investigated using potassium chloride (KCl) and carbachol (CCh). Neurally mediated contractile responses were evoked by electrical field stimulation (EFS) and were recorded in the absence and presence of atropine (1 μM) or NG-Nitro-l-arginine methyl ester (l-NAME; 100 μM).Key ResultsThe myogenic responses to KCl in the jejunum and colon were unaffected by age. In the colon, but not the jejunum, CCh-induced contractile responses were reduced in aged animals. Compared to young baboons, there was enhanced EFS-induced contractility of old baboon jejunal smooth muscle in contrast to the reduced contractility in the colon. The effect of atropine on the EFS response was lower in aged colonic tissue, suggesting reduced participation of acetylcholine. In aged jejunal tissue, higher contractile responses to EFS were found to be due to reduced nitregic inhibition.Conclusions & InferencesThese findings provide key evidence for the importance of intestinal smooth muscle and ENS senescence in age-associated GI motility disorders.

Effect of Masfon-Aloe vera Drink on Intestinal Motility and Transit in Wistar Albino Rats

The effect of Masfon-Aloe vera drink on intestinal transit and motility was investigated in this study. Thirty (30) albino Wistar rats were divided into 2 batches of 15 rats each, batch 1 for intestinal motility, and batch 2 for intestinal transit experiments. Each batch was further divided into three groups of 5 rats each (control, low dose and high dose). All groups were fed with normal rat chow and water for 21 days. In addition, the control received 0.3 ml of normal saline (0.9% NaCl solution) while the low dose (LD) and high dose (HD) experimental groups received Masfon Aloe vera drink (1 ml and 3 ml/kg body weight orally, once daily respectively). The study was carried out at the Department of Physiology, University of Calabar, Nigeria. At the end of the study duration, intestinal motility and transit studies were conducted. Result for intestinal motility showed the extract (Masfon-Aloe vera drink), at either low or high dose did not significantly change the frequency and amplitude of the spontaneous contraction (basal contraction) of the rat ileum when compared with the control. Graded concentrations of Acetylcholine (10 to 10) was observed to produce a dose dependent increase in contraction of the rat ileum which was significantly (p<0.001) greater in the LD and HD groups at lower concentrations of 10 and 10M. The mean percentage intestinal transit which was not Original Research Article British Journal of Medicine & Medical Research, 4(6): 1335-1344, 2014 1336 significantly different (p = 0.226, p=0.892) among the groups was 42.16 ± 2.63 in the low dose, 37.75 ± 5.15 in the high dose groups compared to 36.91 ± 3.01 in the control. Administration of atropine produced significantly higher (p<0.01) relaxations in the LD (5.00 ± 0.41 mm) and HD groups compared with control [relaxation in mm, mean ± SEM (2.25 ± 0.25) in control vs (5.00 ± 0.41) and (10.75 ± 0.25) in LD and HD respectively]. Masfon-Aloe vera drink administered at these concentrations “did” not significantly alter the basal motility and transit of the rat ileum, but was observed to potentiate Ach induced contraction of the rat ileum, and also “augmented” the relaxant effect of atropine.

Atropine for the Treatment of Childhood Myopia: Changes after Stopping Atropine 0.01%, 0.1% and 0.5%

To study the change in spherical equivalent and other ocular parameters 1 year after stopping the administration of atropine. Prospective randomized double-masked clinical trial. We assigned 400 myopic children, 6 to 12 years of age, to receive atropine 0.5%, 0.1% or 0.01% for 24 months, after which medication was stopped. Parents and children gave informed consent to participate in the research. Children were reviewed at 26, 32 and 36 months, and changes in cycloplegic spherical equivalent (SE), axial length (AL), visual acuity, pupil size, and accommodation were assessed. Of the children, 356 (89%) entered into the washout phase. At entry, there was no significant difference in age, gender, SE, or AL among the children in the various atropine groups. Over the following 12 months, myopic progression was greater in the 0.5% eyes (-0.87 ± 0.52 D), compared to the 0.1% (-0.68 ± 0.45 D) and 0.01% eyes (-0.28 ± 0.33 D, P < 0.001). AL growth was also greater in the 0.5% (0.35 ± 0.20 mm) and 0.1% (0.33 ± 0.18 mm) eyes, compared to the 0.01% eyes (0.19 ± 0.13 mm, P < 0.001). Pupil size and near visual acuity returned to pre-atropine levels in all groups, but accommodation at 36 months was less in the 0.5% eyes (13.24 ± 2.72 D) compared to the 0.1% (14.45 ± 2.61 D) and 0.01% eyes (14.04 ± 2.90 D, P < 0.001). The overall increase in SE over the entire 36 months in the 0.5%, 0.1% and 0.01% groups was -1.15 ± 0.81 D, -1.04 ± 0.83 D and -0.72 ± 0.72 D, respectively (P < 0.001). There was a myopic rebound after atropine was stopped, and it was greater in eyes that had received 0.5% and 0.1% atropine. The 0.01% atropine effect, however, was more modulated and sustained.

In-VITRo effect of Ficus deltoidea on the contraction of isolated rat's uteri is mediated via multiple receptors binding and is dependent on extracellular calcium.

BackgroundFicus deltoidea, is a perennial herb that is used to assist labor, firm the uterus post-delivery and to prevent postpartum bleeding. In view of its claimed uterotonic action, the mechanisms underlying plant’s effect on uterine contraction were investigated.MethodsAdult female SD rats were injected with 2 mg/kg 17β-oestradiol (E2) to synchronize their oestrous cycle. A day after injection, uteri were removed for in-vitro contraction studies. The dose dependent effect of Ficus deltoidea aqeous extract (FDA) on the tension produced by the isolated rat’s uteri was determined. The effects of atropine (2×10-8 M), atosiban (0.5 IU), THG113.31 (10 μM), oxodipine (0.25 mM), EDTA (1 mM), 2-amino-ethoxy-diphenylborate (2-APB) (40 mM) and thapsigargin (1 mM) on the maximum force of contraction (Emax) achieved following 2 mg/ml FDA administration were also investigated.ResultsFDA induced in-vitro contraction of the isolated rat’s uteri in a dose-dependent manner. Administration of atropine, atosiban and THG113.31 reduced the Emax with atosiban having the greatest effect. The Emax was also reduced following oxodipine and EDTA administration. There was no significant change observed following 2-APB administration. Thapsigargin, however, augmented Emax.ConclusionsFDA-induced contraction of the isolated rat’s uteri is mediated via multiple uterotonin receptors (muscarinic, oxytocin and prostaglandin F2α) and was dependent on the extracellular Ca2+. Contraction, however, was not dependent on the Ca2+ release from the internal stores. This in-vitro study provides the first scientific evidence on the claimed effect of Ficus Deltoidea on uterine contraction.

Ontogeny and control of the heart rate power spectrum in the last third of gestation in fetal sheep

Power spectral analysis of fetal heart rate variability has been proposed to provide a non-invasive estimate of autonomic balance. However, there are few systematic data before birth. We therefore examined developmental changes in the frequency power spectrum at very low (0-0.04 Hz), low (0.04-0.15 Hz) and high frequencies (0.15-0.4 Hz), as well as the ratio of low- to high-frequency power (LF/HF), in chronically catheterized, healthy fetal sheep at 0.6 (n = 8), 0.7 (n = 7) and 0.8 gestational age (ga; n = 11). In a second study, 0.8 ga fetuses received either atropine (4.8 mg bolus, then 4.8 mg h(-1) for 30 min, n = 6) or 6-hydroxydopamine (20 mg ml(-1) at 2.5 ml h(-1) for 3 h; n = 9). Data were analysed by sleep state, defined by low-voltage-high-frequency (LV) or high-voltage-low-frequency (HV) EEG. Total spectral power increased with gestational age (P < 0.05), while LF/HF decreased from 0.6 to 0.7 ga. At 0.8 ga, heart rate and LF/HF were significantly higher during HV than LV sleep (P < 0.05). Consistent with this, although total spectral power was not significantly greater during HV sleep, there was a significant interaction between sleep state and frequency band (P = 0.02). Both atropine (P = 0.05) and 6-hydroxydopamine (P < 0.05) were associated with an overall reduction in spectral power but no significant effect on the LF/HF ratio. This study does not support substantial, consistent differences between the frequencies of sympathetic and parasympathetic activity in late-gestation fetal sheep.

Effect of fractionated extracts and isolated pure compounds of spondias mombin (&lt;i&gt;L. Anacardiaceae&lt;/i&gt;) leaves on novelty-induced rearing and grooming behaviors in mice.

This study attempted to elucidate the neurotransmitter systems involved in the neurophysiological properties of ethanolic extract, fractions and pure isolates of Spondias mombin leaves in mice (n = 6) after intraperitoneal (i.p.) route of administration.The crude ethanolic extract of Spondian mombin leaves was fractionated using the partitioning method to obtain the ethylacetate, butanolic and aqueous fractions. Open column chromatographic fractionation of the ethylacetate fraction yielded seven sub-fractions, out of which the pure coumaroyl, quercetin and gallic acid derivatives were obtained after purification on Sephadex LH 20. The ethanolic extract, butanolic fraction, ethylacetate subfractions and pure isolates of the Spondian mombin leaves were tested on novelty-induced rearing and grooming behaviours in mice with standard pharmacological tools using the open field method. The extract and its fractions decreased novelty-induced rearing in a dose-dependent manner. While the Coumaroyl derivative had no effect on novelty-induced rearing, it significantly reversed the inhibitory effect of yohimbine, propranolol and haloperidol on novelty-induced rearing. Quercetin significantly potentiated the inhibitory effect of yohimbine on novelty-induced rearing. Naloxone significantly potentiated the quercetin-induced suppression of novelty-induced rearing. Gallic acid derivative significantly potentiated the inhibitory effect of yohimbine on novelty-induced rearing. Naloxone, atropine and haloperidol pretreatments significantly potentiated gallic acid derivative-induced suppression of novelty-induced rearing.The extract and its fractions had biphasic effect on novelty-induced grooming in mice. Coumaroyl derivative significantly increased novelty-induced grooming, while quercetin and gallic acid derivative decreased novelty-induced grooming significantly. The three pure isolates significantly reversed the effects of yohimbine and atropine on the novelty-induced grooming in mice. Propranolol-induced increase in novelty-induced grooming was significantly reversed by coumaroyl and gallic acid derivatives. Pre-treatment with naloxone significantly increased the gallic acid derivative-induced suppression of novelty-induced grooming. Pre-treatment with haloperidol reversed the effect of coumaroyl derivative and potentiated the inhibitory effect of quercetin derivative and gallic acid derivative significantly. This study suggested that adrenergic and dopaminergic neuro-transmissions are strongly involved in the neural mechanisms of the effect of the three pure isolates derivative, while opioid neuro-transmission is strongly linked with the neural mechanism of behavioural effect of coumaroyl derivative.