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Behavioural Effects (behavioural + effects)
Selected AbstractsCONTROLLED TRIAL OF CUMULATIVE BEHAVIOURAL EFFECTS OF A COMMON BREAD PRESERVATIVEJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 7 2003BJ Marshall No abstract is available for this article. [source] Simulating the Behavioural Effects of Welfare Reforms Among Sole Parents in AustraliaTHE ECONOMIC RECORD, Issue 242 2002Alan Duncan This paper derives and estimates an econometric model of labour supply among sole parents in Australia, using modelling techniques which treat the labour supply decision as a utility maximising choice between a given number of discrete states. The model is then used to look at the likely effects of actual and hypothetical welfare policy reforms. Model estimates are based upon net incomes generated by the Melbourne Institute Tax and Transfer Simulator (MITTS), developed at the Melbourne Institute in collaboration with the Department of Family and Community Services (FaCS). [source] Histamine H1 receptor blockade predominantly impairs sensory processes in human sensorimotor performanceBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2009P Van Ruitenbeek Background and purpose:, Centrally active antihistamines impair cognitive performance, particularly sensorimotor performance. The aim of the present study was to further elucidate the scarcely studied subprocesses involved in sensorimotor performance, which may be affected by H1 receptor blockade. Better knowledge about the cognitive deficits associated with histamine dysfunction can contribute to better treatment of clinical disorders in which histamine hypofunction may be a contributing factor, such as in schizophrenia. Experimental approach:, Interactions of dexchlorpheniramine with specific task manipulations in a choice reaction time task were studied. Task demands were increased at the level of sensory subprocesses by decreasing stimulus quality, and at the level of motor subprocesses by increasing response complexity. A total of 18 healthy volunteers (9 female) aged between 18 and 45 years participated in a three-way, double-blind, crossover design. Treatments were single oral doses of 4 mg dexchlorpheniramine, 1 mg lorazepam and placebo. Behavioural effects were assessed by measuring reaction times and effects on brain activity by event-related potentials. Key results:, Dexchlorpheniramine significantly slowed reaction times, but did not significantly interact with task manipulations. However, it did significantly interact with stimulus quality, as measured by event-related potentials. Lorazepam slowed reaction times and interacted with perceptual manipulations, as shown by effects on reaction times. Conclusions and implications:, The results confirm that the histamine system is involved in sensory information processing and show that H1 blockade does not affect motoric information processing. Histamine hypofunction in clinical disorders may cause impaired sensory processing, which may be a drug target. [source] MDMA, methamphetamine and their combination: possible lessons for party drug users from recent preclinical researchDRUG AND ALCOHOL REVIEW, Issue 1 2007KELLY J. CLEMENS Abstract The substituted amphetamines 3,4-methylenedioxymethamphetamine (MDMA, ,Ecstasy') and methamphetamine (METH, ,ice', ,speed') are increasingly popular drugs amongst party-drug users. Studies with humans have investigated the acute and possible long-term adverse effects of these drugs, yet outcomes of such studies are often ambiguous due to a variety of confounding factors. Studies employing animal models have value in determining the acute and long-term effects of MDMA and METH on brain and behaviour. Self-administration studies show that intravenous METH is a particularly potent reinforcer in rats and other species. In contrast, MDMA appears to have powerful effects in enhancing social behaviour in laboratory animals. Brief exposure to MDMA or METH may produce long-term reductions in dopamine, serotonin and noradrenaline in the brain and alterations in the density of various receptor and transporter proteins. However it is still unclear, particularly in the case of MDMA, whether this reflects a ,neurotoxic' effect of the drug. Lasting alterations in social behaviour, anxiety, depressive symptoms and memory have been demonstrated in laboratory rats given MDMA or METH and this matches long-term changes reported in some human studies. Recent laboratory studies suggest that MDMA/METH combinations may produce greater adverse neurochemical and behavioural effects than either drug alone. This is of some concern given recent evidence that party drug users may be frequently exposed to this combination of drugs. [source] Drug education: myth and realityDRUG AND ALCOHOL REVIEW, Issue 1 2001GRAEME HAWTHORNE Abstract Recently there has been an increase in Australian public funds for drug education. The accompanying rhetoric asserts that it is to enable abstinence among young people. This contradicts some State Government education guidelines endorsing harm minimization. A literature search of the key electronic databases, drug agency libraries, the Internet and reference lists identified evaluation research in school-based drug education. There is little evidence to support the new public rhetoric. The predictors of adolescent drug use are social and personal; schools can have little effect on these. Four models of drug education are described. Schools, however, mix-and-match activities from different models, and exposure is too slight for major effects on behaviours. Although methodological difficulties affect findings, none of the drug education models show consistent behavioural effects over time. There is a mismatch between the new public rhetoric and the evaluation research literature. Reasons for this are explored, including that there are two stakeholder groups, one with exaggerated ideological anti-drug messages and the other with more realistic perspectives about what schools can reasonably achieve. The paradox is that the rhetoric is needed for continued funding, yet this same rhetoric sets up criteria which doom drug education to failure. [source] A computerized harm minimization prevention program for alcohol misuse and related harms: randomized controlled trialADDICTION, Issue 4 2009Laura Vogl ABSTRACT Aims Hazardous alcohol use is a leading cause of death among adolescents and young adults world-wide, yet few effective prevention interventions exist. This study was the first to examine a computerized harm minimization intervention to reduce alcohol misuse and related harms in adolescents. Design Cluster randomized controlled trial of a six-session curriculum-integrated harm minimization prevention program. The intervention was delivered by computer in the form of a teenage drama, which provided education through alcohol-related scenarios to which young people could relate. Setting Schools in Australia. Participants A total of 1466 year 8 students (13 years) from 16 high schools in Australia were allocated randomly to a computerized prevention program (n = 611, eight schools) or usual classes (n = 855, eight schools). Measurements Change in knowledge, alcohol use, alcohol-related harms and alcohol expectancies. Findings A computerized prevention program was more effective than usual classes in increasing alcohol-related knowledge of facts that would inform safer drinking choices and decreasing the positive social expectations which students believed alcohol may afford. For females it was effective in decreasing average alcohol consumption, alcohol-related harms and the frequency of drinking to excess (more than four standard drinks; 10 g ethanol). For males the behavioural effects were not significant. Conclusions A harm minimization approach is effective in educating young people about alcohol-related risks and is effective in reducing risky drinking and harms among girls. Reduction of problems among boys remains a challenge. [source] PRECLINICAL STUDY: FULL ARTICLE: Tolerance to 3,4-methylenedioxymethamphetamine is associated with impaired serotonin releaseADDICTION BIOLOGY, Issue 3 2010Karen Jones ABSTRACT Tolerance to the behavioural effects of 3,4-methylenedioxymethamphetamine (MDMA) following high dose exposure has been attributed to alterations in serotonergic systems. The present study aimed to determine whether decreased 5-HT release and/or 5-HT2A/C receptor desensitization might play a role in tolerance by measuring the response to selective ligands following MDMA exposure. To this end, the latency to nose poke and emerge from a hide box to an open field arena following administration of various ligands to MDMA pre-treated and control rats was measured. Acute exposure to MDMA (0.0,3.3 mg/kg), the 5-HT releasing stimulant fenfluramine (0.0,2.0 mg/kg) and the 5-HT2 receptor agonist m-CPP (0.0,1.25 mg/kg) increased nose poke and emergence latency. Following administration of doses that produce 5-HT2A receptor-mediated behaviours, the 5-HT2 receptor agonist (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane failed to alter nose poke and emergence latency, suggesting a limited role of this receptor subtype in these behaviours. Activation of 5-HT2C receptors was implicated in the behavioural response to both MDMA and m-CPP since the increased emergence latency was dose-dependently attenuated by pre-treatment with the selective 5-HT2C receptor antagonist RS102221 (0.0,1.0 mg/kg). Tolerance to the behavioural effect of MDMA and fenfluramine but not m-CPP was produced by prior exposure to MDMA (10 mg/kg administered at two-hour intervals, total 40 mg/kg), and tissue levels of 5-HT and 5-HIAA were decreased. These findings suggest that tolerance to the increased nose poke and emergence latency produced by MDMA is due to impaired 5-HT release. [source] PRECLINICAL STUDY: Atypical development of behavioural sensitization to 3,4-methylenedioxymethamphetamine (MDMA, ,Ecstasy') in adolescent rats and its expression in adulthood: role of the MDMA chiralityADDICTION BIOLOGY, Issue 1 2010Nora Von Ameln ABSTRACT Despite the great popularity of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) as a drug of abuse, not much is known about the detailed mechanisms of the acute and subchronic effects of the drug. There is especially a lack of information about the distinct behavioural effects of its optical isomers (enantiomers) R- and S-MDMA compared with the racemic RS-MDMA. For this purpose, adolescent rats were repetitively treated during two treatment stages (stage 1: days 1,10; stage 2: days 15, 17, 19) with RS-MDMA (5 or 10 mg/kg) or each of the respective enantiomers (5 mg/kg). The repeated treatment started on postnatal day (PND) 32 and locomotor activity was measured on each day by means of a photobeam-equipped activity box system. RS-MDMA or S-MDMA administration led acutely to massive hyperlocomotion and subchronically, to the development of behavioural sensitization after a short habituation period. R-MDMA was free of hyperactivating effects and even decreased locomotor behaviour upon repeated treatment. Nevertheless, co-administration of R-MDMA increased the hyperactivity of S-MDMA and made the S-MDMA induced behavioural sensitization state-dependent. The animals pre-treated with R-MDMA showed a sensitized response in adulthood when tested with RS-MDMA. Our results indicated that even in the absence of substantial neurotoxicity, both MDMA enantiomers can lead to long-term changes in brain circuitry and concomitant behavioural changes when repeatedly administered in adolescence. The sensitization development was most pronounced in the animals treated with S- and RS-MDMA; the animals with R-MDMA did not develop sensitization under repeated treatment but expressed a sensitized response when challenged with RS-MDMA. [source] Tonic regulation of satiety by 5-HT1B receptors in the mouse: converging evidence from behavioural and c- fos immunoreactivity studies?EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2004Michelle D. Lee Abstract Activation of 5-HT1B receptors is thought to play an important role in the inhibitory influence of serotonin on feeding behaviour and body weight in mammals. Earlier studies have shown that 5-HT1B -knockout (KO) mice eat more and are heavier than wild-type (WT) controls and that the selective 5-HT1B receptor agonist CP-94,253 reduces food intake in food-deprived mice. Here we characterize the behavioural effects of both CP-94,253 and the selective 5-HT1B receptor antagonist SB224289 on feeding and other behaviours within the behavioural satiety sequence, and also report a c- fos mapping study using CP-94,253. CP-94,253 produced a dose-dependent suppression of food intake with a profile consistent with a selective effect on feeding behaviour. These effects were absent or reduced in 5-HT1B -KO mice and in WT mice pretreated with SB224289. SB224289 administered alone enhanced food intake consistent with impaired satiation; a similar effect was apparent in 5-HT1B -KO mice compared to WT. CP-94,253 induced c- fos in a range of structures previously implicated in the expression of feeding behaviour. These results suggest that the activation of 5-HT1B receptors is an important component of endogenous satiation mechanisms in the mouse. [source] C-type natriuretic peptide (CNP) regulates cocaine-induced dopamine increase and immediate early gene expression in rat brainEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2001Nathalie Thiriet Abstract The neuropeptide C-type natriuretic peptide (CNP) is the primary biologically active natriuretic peptide in brain. Using in situ hybridization, the present report demonstrates that CNP regulates egr-1, c-fos and junB immediate early gene expression in rat brain. In the frontal cortex, CNP induced immediate early gene expression whereas it inhibited dose-dependently the cocaine-induced early gene expression in the dopaminergic projection fields nucleus accumbens and caudate,putamen. CNP may produce its effect directly on dopaminergic neurons because we found that its receptor, guanylyl cyclase GC-B, was expressed in the mesencephalon where dopaminergic neurons originate, as well as in their projection fields. The inhibition by CNP of the early gene expression elicited by cocaine in the caudate,putamen is correlated with a CNP-evoked decrease in cocaine-induced rise in extracellular dopamine, measured by in vivo microdialysis experiments. The significance of the inhibition of cocaine-induced dopamine release and early gene induction by the endogenous peptide CNP is demonstrated by data indicating that CNP reduced the cocaine-induced spontaneous locomotor activation. By inhibiting dopaminergic neuronal activity, CNP represents a potential negative regulator of related behavioural effects of cocaine. [source] Cortico-cortical connectivity of the human mid-dorsolateral frontal cortex and its modulation by repetitive transcranial magnetic stimulationEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2001Abstract Modulation of cortico-cortical connectivity in specific neural circuits might underlie some of the behavioural effects observed following repetitive transcranial magnetic stimulation (rTMS) of the human frontal cortex. This possibility was tested by applying rTMS to the left mid-dorsolateral frontal cortex (MDL-FC) and subsequently measuring functional connectivity of this region with positron emission tomography (PET) and TMS. The results showed a strong rTMS-related modulation of brain activity in the fronto-cingulate circuit. These results were confirmed in a parallel experiment in the rat using electrical stimulation and field-potential recordings. Future studies are needed to provide a direct link between the rTMS-induced modulation of cortical connectivity and its effects on specific behaviours. [source] Cue usage in financial statement fraud risk assessments: effects of technical knowledge and decision aid useACCOUNTING & FINANCE, Issue 1 2009Jean-Lin Seow M41; M49 Abstract This paper investigates the effects of technical knowledge and decision aid use on financial statement fraud risk assessments made by directors and students. More extreme fraud risk assessments are made when participants identify and process larger (smaller) numbers of diagnostic (non-diagnostic) factors, with technical knowledge driving diagnostic factor identification. Significant decision aid-technical knowledge effects are also found; decision aid use has a detrimental effect on high-knowledge directors while improving performance in inexperienced, low-knowledge students. These results suggest that although decision aids can afford gains in performance in inexperienced users, they can have unintended and/or paradoxical behavioural effects on experienced users. [source] Caffeine levels in saliva: associations with psychosocial factors and behavioural effectsHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 7 2001Carolyn Brice Abstract The present study had two main aims. The first was to examine associations between psychosocial factors, health-related behaviours, regular level of caffeine consumption, time of day and levels of caffeine in saliva following acute caffeine challenges. The second aim was to determine whether individual differences in changes in performance following ingestion of caffeine were related to levels of caffeine in saliva. One hundred and forty-four young adults participated in the study. Questionnaires were administered prior to the study to measure psychosocial characteristics, health-related behaviours and habitual levels of caffeine consumption. Two double-blind acute caffeine challenges were then carried out 1 week apart. Volunteers were given either placebo or 1.5 or 3,mg/kg of caffeine on each occasion. The challenges were carried out at 8,:,00, 11,:,00, 14,:,00 or 18,:,00,h so that the impact of time of day could be assessed. In the week between the two challenges the volunteers consumed either caffeinated or decaffeinated products. This allowed investigation of the effects of caffeine withdrawal on caffeine metabolism. Prior to each caffeine challenge volunteers performed a range of tasks, and a baseline saliva sample was taken. The tasks were repeated 1,h after ingestion of the caffeine, with saliva samples being taken at the start and end of the 1,h test battery. The results showed that the level of caffeine in the saliva was a good indicator of the dose of caffeine consumed and of compliance with the withdrawal manipulation. Caffeine levels were not influenced by time of day, habitual caffeine consumption, psychosocial factors or health-related behaviours. Individual differences in caffeine levels in saliva were not related to the individual variation in the effects of caffeine on performance. Copyright © 2001 John Wiley & Sons, Ltd. [source] The effects of caffeine on simulated driving, subjective alertness and sustained attentionHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 7 2001Carolyn Brice Abstract There is evidence that caffeine increases alertness and reduces fatigue. This may be especially so in low arousal situations (e.g. working at night or for prolonged hours). Caffeine has also been found to improve performance on vigilance tasks and simple tasks requiring sustained response. Again, these effects are often clearest when alertness is reduced, although there is evidence that benefits may still occur when the individual is unimpaired. Most studies to date have investigated the behavioural effects of caffeine in laboratory experiments using artificial tasks. In the current study 3,mg/kg caffeine was found to improve steering accuracy in a 1,h simulated drive. Measures of mood and performance on a sustained attention task also showed the benefits of caffeine. These findings suggest that laboratory results reflect a general benefit of caffeine that may also be observed in real-life situations. Other evidence examining the effects of caffeine on performance efficiency over the working day has shown the benefits of caffeine consumption on measures of sustained attention and alertness. This study also provided evidence suggesting that caffeine is often consumed when alertness is low to maximise alertness and performance efficiency. The implications of these findings for road safety are also considered. Copyright © 2001 John Wiley & Sons, Ltd. [source] Effects of the toxic dinoflagellate, Alexandrium fundyense on three species of larval fish: a food-chain approachJOURNAL OF FISH BIOLOGY, Issue 1 2008J. C. Samson Sublethal behavioural effects of exposure to paralytic shellfish toxins (PST; saxitoxin and its derivatives) from the toxic dinoflagellate Alexandrium fundyense were investigated in newly settled winter flounder Pseudopleuronectes americanus, larval sheepshead minnow Cyprinodon variegatus and larval mummichog Fundulus heteroclitus through an A. fundyense,copepod,fish food chain. Consumption of as few as six to 12 toxin-containing copepods was lethal to the fishes. After consuming fewer toxin-containing copepods, all three fish species exhibited sublethal effects from vector-mediated exposure. Prey-capture ability of mummichogs was reduced in larvae that had consumed toxic copepods, Coullana canadensis. After consuming toxic C. canadensis or mixed copepods, mummichog larvae had reduced swimming performance. Swimming activity was also significantly reduced in winter flounder after consuming toxic copepods, including time spent in motion and distance travelled. Prey capture and predator avoidance were reduced in first-feeding sheepshead minnow larvae that had consumed toxic dinoflagellate cells. Adverse effects on prey capture or predator avoidance may reduce larval survival and facilitate the transmission of PST through the food web. This study provides baseline information on sublethal effects of PST exposure on fishes using a novel food-chain approach with zooplankton as vectors. [source] Cellular and behavioural effects of the adenosine A2a receptor antagonist KW-6002 in a rat model of l -DOPA-induced dyskinesiaJOURNAL OF NEUROCHEMISTRY, Issue 6 2003M. Lundblad Abstract We have examined the ability of KW-6002, an adenosine A2a antagonist, to modulate the dyskinetic effects of l -DOPA in 6-hydroxydopamine-lesioned rats. In animals rendered dyskinetic by a previous course of l -DOPA treatment, KW-6002 did not elicit any abnormal involuntary movements on its own, but failed to reduce the severity of dyskinesia when coadministered with l -DOPA. A second experiment was undertaken in order to study the effects of KW-6002 in l -DOPA-naive rats. Thirty-five animals were allotted to four groups to receive a 21-day treatment with: (i) KW-6002 (10 mg/kg/day); (ii) l -DOPA (6 mg/kg/day) i.p.; (iii) KW-6002 plus l -DOPA (same doses as above) or (iv) vehicle. Chronic treatment with KW-6002-only produced a significant relief of motor disability in the rotarod test in the absence of any abnormal involuntary movements. Combined treatment with l -DOPA and KW-6002 improved rotarod performance to a significantly higher degree than did each of the two drugs alone. However, this combined treatment induced dyskinesia to about the same degree as did l -DOPA alone. In situ hybridization histochemistry showed that KW-6002 treatment alone caused an approximately 20% reduction in the striatal levels of preproenkephalin mRNA, whereas neither the coadministration of KW-6002 and l -DOPA nor l -DOPA alone significantly altered the expression of this transcript in the dopamine-denervated striatum. Either alone or in combination with l -DOPA, KW-6002 did not have any modulatory effect on prodynorphin mRNA expression or FosB/,FosB-like immunoreactivity in the dopamine-denervated striatum. These results show that monotreatment with an adenosine A2a receptor antagonist can relieve motor disability without inducing behavioural and cellular signs of dyskinesia in rats with 6-hydroxydopamine lesions. Cotreatment with KW-6002 and l -DOPA potentiates the therapeutic effect but not the dyskinesiogenic potential of the latter drug. [source] Theoretical Consequences of Fluctuating Versus Constant Liganding of Oestrogen Receptor-, in NeuronesJOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2010D. W. Pfaff A theory is put forward that emphasises differences in neuronal responses to fluctuations in steroid hormone levels compared to constant hormone levels. We propose that neuronal functions that regulate gonadotrophin release from the anterior pituitary tend to be more sensitive to rapid increases in the levels of oestrogens than they are to constant oestrogen levels. By contrast, neurones that control certain behavioral functions are affected just as well by constant oestrogen levels as by positively accelerating levels of oestrogen. In addition to providing examples of data from recent experiments that examine actions of the long-term effects of oestrogen on mouse behaviour, we illustrate the behavioural effects of microinjections of adeno-associated viral vectors of small interfering RNA directed against the mRNA for oestrogen receptor-, (ER,). This manipulation provides for a long-term loss of ER, function in a neuranatomically specific manner. The theoretical distinction between temporal features of oestrogen sensitivity of neuroendocrine versus behavioural function is not absolute, but is intended to stimulate new experimentation that examines temporal features of oestrogen administration. [source] Hypocretin-1 Dose-Dependently Modulates Maternal Behaviour in MiceJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2006K. L. D'Anna Increases in neuronal activity of hypocretin (HCRT), a peptide involved in arousal, and in HCRT-1 receptor mRNA expression have recently been identified in association with lactation. HCRT is released within brain regions regulating maternal behaviour and it is possible that increased HCRT neurotransmission during lactation supports maternal care. The present study examined for the first time the behavioural effects of HCRT on lactating mice. At intermediate doses, intracerebroventricular (i.c.v.) injections of HCRT-1 (0.06 and 0.1 µg) elevated levels of licking and grooming of pups (but not self-grooming) and number of nursing bouts without affecting other behaviours. At the highest dose, HCRT-1 (0.3 µg, i.c.v) delayed latency to nurse, decreased nursing, increased time off nest, and decreased maternal aggression. Intraperitoneal injections of the HCRT-1 receptor antagonist, SB-334867, exhibited a general trend towards increasing time spent low-arched back nursing (P = 0.053) and decreasing licking and grooming of pups while high-arched back nursing (P = 0.052). This suggests that the endogenous release of HCRT, working independently or dependently with other neuromodulators, may be necessary for full maternal behaviour expression. Possible sites of HCRT action in enhancing and impairing maternal care were identified via examinations of c,Fos immunoreactivity in association with i.c.v. HCRT injections. Together, these finding support the idea of HCRT modulating maternal behaviour, with intermediate levels (0.06 and 0.1 µg) supporting (even augmenting) some behaviours, but with levels that are too high (0.3 µg HCRT, i.c.v.), maternal behaviour and aggression are suppressed. [source] Controlled trial of cumulative behavioural effects of a common bread preservative,JOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 4 2002S Dengate Objective: Many anecdotes and one scientific report describe cumulative behavioural effects of bread preservative on children. Methodology: Twenty-seven children, whose behaviour improved significantly on the Royal Prince Alfred Hospital diet, which excludes food additives, natural salicylates, amines and glutamates, were challenged with calcium propionate (preservative code 282) or placebo through daily bread in a double-blind placebo-controlled crossover trial. Results: Due to four placebo responders, there was no significant difference by anova of weighted placebo and challenge Rowe Behaviour Rating Inventory means, but a statistically significant difference existed in the proportion of children whose behaviours ,worsened' with challenge (52%), compared to the proportion whose behaviour ,improved' with challenge (19%), relative to placebo (95% confidence intervals 14,60%). Conclusions: Irritability, restlessness, inattention and sleep disturbance in some children may be caused by a preservative in healthy foods consumed daily. Minimizing the concentrations added to processed foods would reduce adverse reactions. Testing for behavioural toxicity should be included in food additive safety evaluation. [source] Effects of oral administration of extracts of Hypericum perforatum (St John's wort) on brain serotonin transporter, serotonin uptake and behaviour in miceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 12 2004Kazufumi Hirano The pharmacological effects of extracts of Hypericum perforatum (St John's wort) were characterized in-vitro and ex-vivo, in relation to its behavioural effects. In in-vitro experiments, St John's wort inhibited brain synaptosomal [3H]serotonin uptake in mice with little effect on specific [3H]paroxetine binding. For selective serotonin-reuptake inhibitors (SSRIs), the IC50 value for [3H]serotonin uptake (molar concentration of unlabelled drug necessary to displace 50% of specific uptake) correlated well with the inhibition constant Ki value for [3H]paroxetine binding in mouse brain. Oral administration of St John's wort (900 mg kg,1), paroxetine (1 mg kg,1) and sertraline (10 mg kg,1) brought about significant increases in the Km value for [3H]serotonin uptake into brain synaptosomes 4 h later, and only SSRIs suppressed specific [3H]paroxetine binding in mouse brain. St John's wort and SSRIs significantly inhibited marble-burying behaviour in mice and the time-course of attenuation of this behaviour by St John's wort was similar to that of [3H]serotonin uptake inhibition. In the forced swimming test, St John's wort, but not SSRIs, suppressed the immobility time of mice after oral administration. These results provide the first in-vivo evidence to suggest that the mode of antidepressant action of St John's wort differs from that of SSRIs. Thus, this study may have a significant impact on phytotherapy with St John's wort. [source] Oral administration of a centrally acting ghrelin receptor agonist to conscious rats triggers defecationNEUROGASTROENTEROLOGY & MOTILITY, Issue 1 2009A. D. Shafton Abstract, Agonists of ghrelin receptors that cross the blood,brain barrier, but not ghrelin itself, administered peripherally (intravenous or subcutaneous), cause defecation by acting on centres in the lumbo-sacral spinal cord. It is not established whether orally administered ghrelin receptor agonists can have this action. We tested GSK894281 for its effectiveness at the ghrelin receptor and its ability to cross the blood,brain barrier. GSK894281 was effective at the human and rat ghrelin receptors at 1,10 nmol L,1, but was >1000-fold less potent at the motilin receptor. It achieved a similar blood concentration by oral or intravenous administration. Oral bioavailability was 74% and brain : blood ratio at steady state was 0.7 : 1. GSK894281 administered orally (1,100 mg kg,1) caused a prompt, dose-related production of faecal pellets; at 10 mg kg,1 faecal output was four times greater than after carrier. The output was the greatest in the first half hour and subsided over the next 90 min. At an oral dose of 10 mg kg,1, the compound was effective on eight successive days. Faecal output was, on average, increased threefold over control in the 2 h after administration on each of the 8 days. This dose also significantly increased food consumption. Rats showed no adverse behavioural effects to the drug on a single application, but at the end of a week of administration they avoided the gavaging pipette. Oral administration of ghrelin receptor agonists that enter the central nervous system could possibly be used to relieve acute cases of constipation or to clear the bowel for colonoscopy. [source] Brain neurotransmitter receptor binding and nootropic studies on Indian Hypericum perforatum Linn.PHYTOTHERAPY RESEARCH, Issue 3 2002Vikas Kumar Abstract The high affinity binding sites for serotonin and benzodiazepine in the frontal cortex, for dopamine in the striatum and muscarinic cholinergic receptors in the hippocampus were investigated in the brains of Charles Foster rats treated for 3 days. Transfer latency on elevated plus maze (TL), passive and active avoidance behaviour (PA and AA) and electroconvulsive shock (ECS) induced amnesia were also studied. Pilot studies indicated that single dose administration of Indian Hypericum perforatum (IHp) had little or no acute behavioural effects and hence the extract of IHp was administered orally at two dose levels (100 and 200,mg/kg, p.o.) once daily for 3 consecutive days, while piracetam (500,mg/kg, i.p.), a clinically used nootropic agent, was administered acutely to rats as the standard nootropic agent. Control rats were treated with an equal volume of vehicle (0.3%,carboxymethyl cellulose). The results indicate that IHp treatment caused a significant decrease in the binding of [3H] spiroperone (DA-D2 receptor) to the striatum and an increase in the binding of [3H] ketanserin (5-HT2A receptor) and [3H] flunitrazepam (BDZ receptor) to the frontal cortex in rats. Preliminary pharmacological studies with IHp extract indicate the presence of two major behavioural actions, namely, antidepressant and anxiolytic. The present findings tend to elucidate the mechanism of earlier observations, the downregulation of the dopamine D2 receptor being consonant with anxiolytic and the upregulation of 5-HT2A and BDZ receptors being consonant with antidepressant activity. Piracetam when given alone, shortened the TL on days 1, 2 and 9 day and also antagonized the amnesic effects of ECS on the TL significantly, whereas IHp antagonized the amnesia produced by ECS. IHp had no significant effect per se on the retention of the PA in rats but produced a significant reversal of ECS induced PA retention deficit. Piracetam showed a significant facilitatory effect per se on PA retention and also reversed the ECS induced impaired PA retention. In the AA test, piracetam facilitated the acquisition and retention of AA in rats but IHp had no effect per se. Both the doses of IHp and piracetam significantly attenuated the ECS induced impaired retention of AA. These results indicate a possible nootropic action of IHp in amnesic animals, which was comparable qualitatively to piracetam. Copyright © 2002 John Wiley & Sons, Ltd. [source] Flattening the Effective Marginal Tax Rate Structure in Australia: Policy Simulations Using the Melbourne Institute Tax and Transfer SimulatorTHE AUSTRALIAN ECONOMIC REVIEW, Issue 2 2003John Creedy This article uses the Melbourne Institute Tax and Transfer Simulator to examine the effects of a reduction in the means-tested benefit taper, or withdrawal, rates in Australia to 30 per cent. That is, all taper rates of 50 per cent and 70 per cent in the March 1998 benefit system are reduced to 30 per cent, while leaving all basic benefit levels unchanged. This change is therefore expected to ,flatten' the tax structure by reducing the high marginal tax rates applying to those with relatively low incomes and increasing the marginal tax rates of medium incomes. Simulations in which all individuals are assumed to remain at their pre-reform labour supply levels are compared with behavioural simulations in which the majority of individuals are free to adjust the number of hours worked. The results reflect only the supply side of the labour market. The database used is the 1997-98 Survey of Income and Housing Costs, so that weekly incomes are based on the financial year 1997-98. The comparison shows that, for sole parents, accounting for behavioural effects of the reform results in a lower estimated expenditure for government, whereas for couples, accounting for behavioural effects results in a higher estimated expenditure. [source] Antinociceptive effect of a ruthenium complex in miceAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 4 2008M. P. Cristiano Summary 1,The ruthenium complexes are important tools in inorganic chemistry. Different biological properties are found in the presence of distinct coordinate ligands, which offer a variety of potential clinical and pharmacological uses. 2,The aim of this work was to evaluate the antinociceptive and behavioural effects of the ruthenium complex, trans -[RuCl2(i-dinic)4]Cl, in mice. 3,The potential analgesic activity was tested using the formalin and hot plate tests and the behavioural effect was evaluated using the rotarod and spontaneous locomotor tests. The complex was administered at concentrations of 1.3, 4.5 and 18.0 ,mol kg,1 i.p. Morphine (6.0 mg kg,1, i.p.) and diclofenac sodium (20.0 mg kg,1, i.p.) were used as reference drugs. 4,The compound had no sedative activity on motor ataxia in the behavioural and analgesic tests. No significant effect was observed in the first phase of the formalin test, however, an effect was observed in the second phase. 5,The complex studied was probably more powerful than the reference drugs as an antinociceptive agent, as this mechanism also involved the nitric oxide (NO) pathway. From this perspective, further experimental studies will be useful to understand the effect of these compounds on NO and the relationship between prostaglandin and NO biosynthesis. [source] Chronic Administration of Ketamine Elicits Antidepressant-Like Effects in Rats without Affecting Hippocampal Brain-Derived Neurotrophic Factor Protein LevelsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2008Lêda S. Garcia The present study was aimed to evaluate behavioural and molecular effects of the chronic treatment with ketamine and imipramine in rats. To this aim, rats were 14 days treated once a day with ketamine (5, 10 and 15 mg/kg) and imipramine (10, 20 and 30 mg/kg) and then subjected to the forced swimming and open-field tests. Ketamine and imipramine, at the all doses tested, reduced immobility time, and increased both climbing and swimming time of rats compared to the saline group, without affecting spontaneous locomotor activity. Brain-derived neurotrophic factor (BDNF) hippocampal levels were assessed in imipramine- and ketamine-treated rats by ELISA sandwich assay. Chronic administration of both drugs, ketamine and imipramine, did not modify BDNF protein levels in the rat hippocampus. In conclusion, our findings demonstrate for the first time that chronic administration of acute inactive doses of ketamine (5 mg/kg) becomes active after chronic treatment, while no signs of tolerance to the behavioural effects of ketamine were observed after chronic administration of acute active doses (10 and 15 mg/kg). Finally, these findings further support the hypothesis that NMDA receptor could be a new pharmacological target for the treatment of mood disorders. [source] Bringing the brain into the test tube: an experiment illustrating the effect of ethanol on nerve terminal viabilityBIOCHEMISTRY AND MOLECULAR BIOLOGY EDUCATION, Issue 3 2001Rodrigo A. Cunha Abstract Ethanol is primarily responsible for the behavioural effects of acute alcoholic beverage consumption, which involves central nervous system dysfunction. The mechanisms of ethanol action in the nervous system are poorly understood, particularly those related to the neurotoxicity of high acute ethanol consumption. We now describe a simple experiment showing that a concentration of ethanol, which is reached in the plasma after high acute ethanol intake, disrupts rat brain nerve terminals, as measured by the release of lactate dehydrogenase. This cytolytic action of ethanol was further enhanced upon depolarisation of the nerve terminals suggesting that the mechanism of action of ethanol might not be related to modification of lipid bilayer properties. © 2001 IUBMB. Published by Elsevier Science Ltd. All rights reserved. [source] Pharmacokinetics of sertindole and its metabolite dehydrosertindole in rats and characterization of their comparative pharmacodynamics based on in vivo D2 receptor occupancy and behavioural conditioned avoidance responseBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 4 2009Christoffer Bundgaard Abstract The objectives of this study were to characterize the pharmacokinetics of sertindole and its active metabolite dehydrosertindole in rats and to evaluate the central modulatory and behavioural pharmacodynamics including a competitive interaction model between the compounds. Following oral administration of sertindole or dehydrosertindole, the plasma concentration,time courses were determined in conjunction with striatal dopamine D2 receptor binding. In addition, the behavioural effects were recorded in the conditioned avoidance response (CAR) paradigm. A one-compartment model with Michaelis-Menten elimination best described the pharmacokinetics of sertindole. Formation of dehydrosertindole was incorporated into the pharmacokinetic model and exhibited first-order elimination. PK/PD modelling after administration of dehydrosertindole resulted in potency estimates of 165 and 424,ng/ml for D2 -occupancy (Kd) and CAR measurements (EC50), respectively. The pharmacokinetics of the parent,metabolite system was integrated into a competitive pharmacodynamic Emax model in order to quantitate the potency of sertindole with the pharmacodynamic parameters of the metabolite taken into account. Based on this approach, effect compartment concentrations of sertindole needed to attain 50% occupancy and half-maximal effect in the CAR paradigm were 133 and 338,ng/ml, respectively. The corresponding potency-estimates obtained after conventional modelling of the sertindole data without accounting for the metabolite amounted to 102 and 345,ng/ml. Based on competitive PK/PD analysis of the parent,metabolite interaction, the relative contribution of dehydrosertindole to the overall pharmacological effect after sertindole administration in rats appeared to be of minor significance. This could mainly be ascribed to the relatively low extent of bioconversion of sertindole into dehydrosertindole in this species. Copyright © 2009 John Wiley & Sons, Ltd. [source] Long-term behavioural outcomes of pre-school mild traumatic brain injuryCHILD: CARE, HEALTH AND DEVELOPMENT, Issue 1 2010A. McKinlay Abstract Background Mild traumatic brain injury (MTBI) is a leading cause of injury for children during their pre-school years. However, there is little information regarding the long-term outcomes of these injuries. Method We used fully prospective data from an epidemiological study of a birth cohort to examine behavioural effects associated with MTBI during the pre-school years. Cases of confirmed MTBI were divided into two groups, those that had received outpatient medical attention, and those that had been admitted to hospital for a brief period of observation (inpatient cases). The remainder of the cohort served as a reference control group. Results Mother/teacher ratings for behaviours associated with attention deficit/hyperactivity disorder and oppositional defiant/conduct disorder, obtained yearly from age 7 to 13, revealed evidence of deficits after inpatient MTBI (n = 21), relative to more minor outpatient injury MTBI (n = 55) and the reference control group (n = 852). For the inpatient group there was evidence of increasing deficits over years 7,13. Conclusions More severe pre-school MTBI may be associated with persistent negative effects in terms of psychosocial development. The vulnerability of pre-school children to MTBI signals a pressing need to identify high-risk cases that may benefit from monitoring and early intervention. [source] | |||||||||||||||||||