scholarly journals Neuroadaptive Changes in  5-HT1A Autoreceptor Sensitivity  Following High-Dose MDMA Treatment

2021 ◽  
Author(s):  
◽  
Simon David Fisher

<p>Rationale: There is evidence that the serotonin (5-HT) deficits and related cognitive and mood impairments caused by +/-3,4- methylenedioxymethamphetamine (MDMA) may be mediated by neuroadaptations of the 5-HT1A autoreceptor. Objectives: The increase in sensitivity of the 5-HT1A autoreceptor caused by highdose, repeated MDMA treatment was assessed neurochemically, by measuring 5- HTP accumulation, and physiologically, via changes in body temperature. Methods: Experiment 1 confirmed the effects of 8-hydroxy-2-(di-npropylamino) tetralin (8-OH-DPAT) (0, 0.025, 0.05, 0.1 mg/kg s.c.) on 5- hydroxytryptophan (5-HTP) accumulation following 3-hydroxybenzylhydrazine dihydrochloride (NSD-1015) administration as a valid measure of 5-HT synthesis and hence 5-HT1A autoreceptor sensitivity in rats. Experiment 2 performed these procedures in additional animals, with half receiving MDMA (4x 10 mg/kg i.p. at 2 hour intervals) two weeks before testing. Body temperature changes due to the 8-OH-DPAT hypothermic response were tested using a rectal probe. Experiment 2b repeated the procedures in additional groups with lower doses of 8-OH-DPAT (0.0125 and 0.00625 mg/kg s.c.). Results: No significant changes in 5-HTP accumulation levels or changes in the hypothermic response to 8-OH-DPAT were found between MDMA pretreated rats and controls in Experiments 2 and 2b. Moreover, there was no substantial evidence of expected 5-HT deficits due to high-dose MDMA treatment. Conclusion: The results do not indicate an increase in sensitivity of the 5-HT1A autoreceptor, and hence the original hypothesis is not supported. However, there were a number of methodological issues, as indicated by the lack of MDMAinduced 5-HT deficits, which prevent a firm conclusion from being drawn. Future research is outlined to overcome these issues.</p>

2021 ◽  
Author(s):  
◽  
Simon David Fisher

<p>Rationale: There is evidence that the serotonin (5-HT) deficits and related cognitive and mood impairments caused by +/-3,4- methylenedioxymethamphetamine (MDMA) may be mediated by neuroadaptations of the 5-HT1A autoreceptor. Objectives: The increase in sensitivity of the 5-HT1A autoreceptor caused by highdose, repeated MDMA treatment was assessed neurochemically, by measuring 5- HTP accumulation, and physiologically, via changes in body temperature. Methods: Experiment 1 confirmed the effects of 8-hydroxy-2-(di-npropylamino) tetralin (8-OH-DPAT) (0, 0.025, 0.05, 0.1 mg/kg s.c.) on 5- hydroxytryptophan (5-HTP) accumulation following 3-hydroxybenzylhydrazine dihydrochloride (NSD-1015) administration as a valid measure of 5-HT synthesis and hence 5-HT1A autoreceptor sensitivity in rats. Experiment 2 performed these procedures in additional animals, with half receiving MDMA (4x 10 mg/kg i.p. at 2 hour intervals) two weeks before testing. Body temperature changes due to the 8-OH-DPAT hypothermic response were tested using a rectal probe. Experiment 2b repeated the procedures in additional groups with lower doses of 8-OH-DPAT (0.0125 and 0.00625 mg/kg s.c.). Results: No significant changes in 5-HTP accumulation levels or changes in the hypothermic response to 8-OH-DPAT were found between MDMA pretreated rats and controls in Experiments 2 and 2b. Moreover, there was no substantial evidence of expected 5-HT deficits due to high-dose MDMA treatment. Conclusion: The results do not indicate an increase in sensitivity of the 5-HT1A autoreceptor, and hence the original hypothesis is not supported. However, there were a number of methodological issues, as indicated by the lack of MDMAinduced 5-HT deficits, which prevent a firm conclusion from being drawn. Future research is outlined to overcome these issues.</p>


2012 ◽  
Vol 26 (2) ◽  
Author(s):  
Joanna Pawlak ◽  
Paweł Zalewski ◽  
Jacek J. Klawe ◽  
Monika Zawadka ◽  
Anna Bitner ◽  
...  

2016 ◽  
Vol 35 (3) ◽  
pp. 1-32 ◽  
Author(s):  
Roger Simnett ◽  
Elizabeth Carson ◽  
Ann Vanstraelen

SUMMARY We present a comprehensive review of the 130 international archival auditing and assurance research articles that were published in eight leading accounting and auditing journals for 1995–2014. In order to support evidence-based international standard setting and regulation, and to identify what has been learned to date, we map this research to the International Auditing and Assurance Standards Board's (IAASB) Framework for Audit Quality. For the areas that have been well researched, we provide a summary of the findings and outline how they can inform standard setters and regulators. We also observe a significant evolution in international archival research over the 20 years of our study, as evidenced by the measures of audit quality, data sources used, and approaches used to address endogeneity concerns. Finally, we identify some challenges in undertaking international archival auditing and assurance research and identify opportunities for future research. Our review is of interest to researchers, practitioners, and standard setters/regulators involved in international auditing and assurance activities.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 189
Author(s):  
Zhanying Zheng ◽  
Sharon Shui Yee Leung ◽  
Raghvendra Gupta

Dry powder inhaler (DPI) is a device used to deliver a drug in dry powder form to the lungs. A wide range of DPI products is currently available, with the choice of DPI device largely depending on the dose, dosing frequency and powder properties of formulations. Computational fluid dynamics (CFD), together with various particle motion modelling tools, such as discrete particle methods (DPM) and discrete element methods (DEM), have been increasingly used to optimise DPI design by revealing the details of flow patterns, particle trajectories, de-agglomerations and depositions within the device and the delivery paths. This review article focuses on the development of the modelling methodologies of flow and particle behaviours in DPI devices and their applications to device design in several emerging fields. Various modelling methods, including the most recent multi-scale approaches, are covered and the latest simulation studies of different devices are summarised and critically assessed. The potential and effectiveness of the modelling tools in optimising designs of emerging DPI devices are specifically discussed, such as those with the features of high-dose, pediatric patient compatibility and independency of patients’ inhalation manoeuvres. Lastly, we summarise the challenges that remain to be addressed in DPI-related fluid and particle modelling and provide our thoughts on future research direction in this field.


1975 ◽  
Vol 53 (6) ◽  
pp. 679-685 ◽  
Author(s):  
J. B. Holter ◽  
W. E. Urban Jr. ◽  
H. H. Hayes ◽  
H. Silver ◽  
H. R. Skutt

Six adult white-tailed deer (Odocoileus virginianus borealis) were exposed to 165 periods of 12 consecutive hours of controlled constant ambient temperature in an indirect respiration calorimeter. Temperatures among periods varied from 38 to 0 (summer) or to −20C (fall, winter, spring). Traits measured were energy expenditure (metabolic rate), proportion of time spent standing, heart rate, and body temperature, the latter two using telemetry. The deer used body posture extensively as a means of maintaining body energy equilibrium. Energy expenditure was increased at low ambient temperature to combat cold and to maintain relatively constant body temperature. Changes in heart rate paralleled changes in energy expenditure. In a limited number of comparisons, slight wind chill was combatted through behavioral means with no effect on energy expenditure. The reaction of deer to varying ambient temperatures was not the same in all seasons of the year.


1961 ◽  
Vol 38 (2) ◽  
pp. 301-314 ◽  
Author(s):  
BODIL NIELSEN

1. In two species of Lacerta (L. viridis and L. sicula) the effects on respiration of body temperature (changes in metabolic rate) and of CO2 added to the inspired air were studied. 2. Pulmonary ventilation increases when body temperature increases. The increase is brought about by an increase in respiratory frequency. No relationship is found between respiratory depth and temperature. 3. The rise in ventilation is provoked by the needs of metabolism and is not established for temperature regulating purposes (in the temperature interval 10°-35°C). 4. The ventilation per litre O2 consumed has a high numerical value (about 75, compared to about 20 in man). It varies with the body temperature and demonstrates that the inspired air is better utilized at the higher temperatures. 5. Pulmonary ventilation increases with increasing CO2 percentages in the inspired air between o and 3%. At further increases in the CO2 percentage (3-13.5%) it decreases again. 6. At each CO2 percentage the pulmonary ventilation reaches a steady state after some time (10-60 min.) and is then unchanged over prolonged periods (1 hr.). 7. The respiratory frequency in the steady state decreases with increasing CO2 percentages. The respiratory depth in the steady state increases with increasing CO2 percentages. This effect of CO2 breathing is not influenced by a change in body temperature from 20° to 30°C. 8. Respiration is periodically inhibited by CO2 percentages above 4%. This inhibition, causing a Cheyne-Stokes-like respiration, ceases after a certain time, proportional to the CO2 percentage (1 hr. at 8-13% CO2), and respiration becomes regular (steady state). Shift to room air breathing causes an instantaneous increase in frequency to well above the normal value followed by a gradual decrease to normal values. 9. The nature of the CO2 effect on respiratory frequency and respiratory depth is discussed, considering both chemoreceptor and humoral mechanisms.


PEDIATRICS ◽  
1963 ◽  
Vol 32 (4) ◽  
pp. 691-702
Author(s):  
Sid Robinson

The central body temperature of a man rises gradually during the first half hour of a period of work to a higher level and this level is precisely maintained until the work is stopped; body temperature then slowly declines to the usual resting level. During prolonged work the temperature regulatory center in the hypothalamus appears to be reset at a level which is proportional to the intensity of the work and this setting is independent of environmental temperature changes ranging from cold to moderately warm. In hot environments the resistance to heat loss may be so great that all of the increased metabolic heat of work cannot be dissipated and the man's central temperature will rise above the thermostatic setting. If this condition of imbalance is continued long enough heat stroke will ensue. We have found that in a 3 mile race lasting only 14 minutes on a hot summer day a runner's rectal temperature may rise to 41.1°C., with heat stroke imminent. The physiological regulation of body temperature of men in warm environments and during the increased metabolic heat production of work is dependent on sweating to provide evaporative cooling of the skin, and on adjustments of cutaneous blood flow which determine the conductance of heat from the deeper tissues to the skin. The mechanisms of regulating these responses during work are complex and not entirely understood. Recent experiments carried out in this laboratory indicate that during work, sweating may be regulated by reflexes originating from thermal receptors in the veins draining warm blood from the muscles, summated with reflexes from the cutaneous thermal receptors, both acting through the hypothalamic center, the activity of which is increased in proportion to its own temperature. At the beginning of work the demand for blood flow to the muscles results in reflex vasoconstriction in the skin. As the body temperature rises the thermal demand predominates and the cutaneous vessels dilate, increasing heat conductance to the skin. Large increments in cardiac output and compensatory vasoconstriction in the abdominal viscera make these vascular adjustments in work possible without circulatory embarrassment.


Author(s):  
Sedef Uzuner

This paper reviews past research that focused on questions of culture in distance learning. Of specific interest are the studies that examined the influence of culture on students’ learning and engagement in asynchronous learning networks (ALNs). The purpose of this review is three-fold: to present the state of knowledge concerning the questions of culture in distance learning, to highlight important methodological issues that past research has left unresolved, and to provide practical insights into teaching culturally and linguistically diverse online communities of learners. For these purposes, 27 studies are examined and the findings are reported under the following categories: What do studies focusing on questions of culture in distance learning tell us? What implications do they suggest for practice and future research? Also, the paper provides methodological insights for researchers who wish to investigate the cultural dimensions of distance learning in future studies.


1989 ◽  
Vol 10 (1) ◽  
pp. 5-32 ◽  
Author(s):  
GAY C. KITSON ◽  
KAREN BENSON BABRI ◽  
MARY JOAN ROACH ◽  
KATHLEEN S. PLACIDI

Authors have commented upon the theoretical similarities in adjustment to widowhood and divorce, but little research has empirically explored this issue. This review examines studies of adjustment to widowhood and/or divorce and points out those places where findings are similar or different. The impact upon adjustment of cause of death or divorce, timing of the event, demographic correlates, economic issues, social support, and attachment is explored. The review concludes with a discussion of methodological issues and topics for future research in widowhood and divorce adjustment research.


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