Role of dopamine–adenosine interactions in the brain circuitry regulating effort-related decision making: insights into pathological aspects of motivation

Brain dopamine, particularly in the nucleus accumbens, has been implicated in activational aspects of motivation and effort-related processes. Accumbens dopamine depletions reduce the tendency of rats to work for food, and alter effort-related decision making, but leave aspects of food motivation such as appetite intact. Recent evidence indicates that the purine neuromodulator adenosine, largely through actions on adenosine A2A receptors, also participates in regulating effort-related processes. Adenosine A2A antagonists can reverse the effects of dopamine D2 antagonists on effort-related choice, and intra- accumbens injections of adenosine A2A agonists produce effects that are similar to those induced by accumbens dopamine depletion or antagonism. These studies have implications for the understanding and treatment of energy-related disorders such as anergia and fatigue in psychiatry and neurology

The effectiveness of an online support group for members of the community with depression: a randomised controlled trial

Background: Internet support groups (ISGs) are popular, particularly among people with depression, but there is little high quality evidence concerning their effectiveness. Aim: The study aimed to evaluate the efficacy of an ISG for reducing depressive symptoms among community members when used alone and in combination with an automated Internet-based psychotherapy training program. Method: Volunteers with elevated psychological distress were identified using a community-based screening postal survey. Participants were randomised to one of four 12-week conditions: depression Internet Support Group (ISG), automated depression Internet Training Program (ITP), combination of the two (ITP+ISG), or a control website with delayed access to ecouch at 6 months. Assessments were conducted at baseline, post-intervention, 6 and 12 months. Results: There was no change in depressive symptoms relative to control after 3 months of exposure to the ISG. However, both the ISG alone and the combined ISG+ITP group showed significantly greater reduction in depressive symptoms at 6 and 12 months follow-up than the control group. The ITP program was effective relative to control at post-intervention but not at 6 months. Conclusions: ISGs for depression are promising and warrant further empirical investigation.The trial was funded by a National Health and Medical Research Council Project Grant 471435. KG is supported by NHMRC Fellowship No. 525413 and HC is supported by Fellowship No. 525411. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Intra-accumbens injections of the adenosine A(2A) agonist CGS 21680 affect effort-related choice behavior in rats

Rationale: Nucleus accumbens dopamine (DA) participates in the modulation of instrumental behavior, including aspects of behavioral activation and effort-related choice behavior. Rats with impaired accumbens DA transmission reallocate their behavior away from food-reinforced activities that have high response requirements, and instead select less-effortful types of food-seeking behavior. Although accumbens DA is considered a critical component of the brain circuitry regulating effort-related processes, emerging evidence also implicates adenosine A2A receptors. Objective: The present work was undertaken to test the hypothesis that accumbens A2A receptor stimulation would produce effects similar to those produced by DA depletion or antagonism. Methods: Three experiments assessed the effects of the adenosine A2A agonist CGS 21680 on performance of a concurrent choice task (lever pressing for preferred food vs. intake of less preferred chow) that is known to be sensitive to DA antagonists and accumbens DA depletions. Results: Systemic injections of CGS 21680 reduced lever pressing but did not increase feeding. In contrast, bilateral infusions of the adenosine A2A receptor agonist CGS 21680 (6.0- 24.0 ng) into the nucleus accumbens decreased lever pressing for the preferred food, but substantially increased consumption of the less preferred chow. Injections of CGS 21680 into a control site dorsal to the accumbens were ineffective. Conclusions: Taken together, these results are consistent with the hypothesis that local stimulation of adenosine A2A receptors in nucleus accumbens produces behavioral effects similar to those induced by accumbens DA depletions. Accumbens adenosine A2A receptors appear to be a component of the brain circuitry regulating effort-related choice behavio

An observing system simulation experiment for the calibration and validation of the surface water ocean topography sea surface height measurement using in situ platforms

Author Posting. © American Meteorological Society, 2018. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Atmospheric and Oceanic Technology 35 (2018): 281-297, doi:10.1175/JTECH-D-17-0076.1.The wavenumber spectrum of sea surface height (SSH) is an important indicator of the dynamics of the ocean interior. While the SSH wavenumber spectrum has been well studied at mesoscale wavelengths and longer, using both in situ oceanographic measurements and satellite altimetry, it remains largely unknown for wavelengths less than ~70 km. The Surface Water Ocean Topography (SWOT) satellite mission aims to resolve the SSH wavenumber spectrum at 15–150-km wavelengths, which is specified as one of the mission requirements. The mission calibration and validation (CalVal) requires the ground truth of a synoptic SSH field to resolve the targeted wavelengths, but no existing observational network is able to fulfill the task. A high-resolution global ocean simulation is used to conduct an observing system simulation experiment (OSSE) to identify the suitable oceanographic in situ measurements for SWOT SSH CalVal. After fixing 20 measuring locations (the minimum number for resolving 15–150-km wavelengths) along the SWOT swath, four instrument platforms were tested: pressure-sensor-equipped inverted echo sounders (PIES), underway conductivity–temperature–depth (UCTD) sensors, instrumented moorings, and underwater gliders. In the context of the OSSE, PIES was found to be an unsuitable tool for the target region and for SSH scales 15–70 km; the slowness of a single UCTD leads to significant aliasing by high-frequency motions at short wavelengths below ~30 km; an array of station-keeping gliders may meet the requirement; and an array of moorings is the most effective system among the four tested instruments for meeting the mission’s requirement. The results shown here warrant a prelaunch field campaign to further test the performance of station-keeping gliders.The authors would like to acknowledge the funding sources: the SWOT mission (JW, LF, DM); NASA Projects NNX13AE32G, NNX16AH76G, and NNX17AH54G (TF); and NNX16AH66G and NNX17AH33G (BQ). AF and MF were funded by the Keck Institute for Space Studies (which is generously supported by the W. M. Keck Foundation) through the project Science-driven Autonomous and Heterogeneous Robotic Networks: A Vision for Future Ocean Observations (http://kiss.caltech.edu/?techdev/seafloor/seafloor.html).2018-08-0

Quasi-biweekly mode of the Asian summer monsoon revealed in Bay of Bengal surface observations

Author Posting. © American Geophysical Union, 2020. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Oceans 125(12),(2020): e2020JC016271, https://doi.org/10.1029/2020JC016271.Asian summer monsoon has a planetary‐scale, westward propagating “quasi‐biweekly” mode of variability with a 10–25 day period. Six years of moored observations at 18°N, 89.5°E in the north Bay of Bengal (BoB) reveal distinct quasi‐biweekly variability in sea surface salinity (SSS) during summer and autumn, with peak‐to‐peak amplitude of 3–8 psu. This large‐amplitude SSS variability is not due to variations of surface freshwater flux or river runoff. We show from the moored data, satellite SSS, and reanalyses that surface winds associated with the quasi‐biweekly monsoon mode and embedded weather‐scale systems, drive SSS and coastal sea level variability in 2015 summer monsoon. When winds are calm, geostrophic currents associated with mesoscale ocean eddies transport Ganga‐Brahmaputra‐Meghna river water southward to the mooring, salinity falls, and the ocean mixed layer shallows to 1–10 m. During active (cloudy, windy) spells of quasi‐biweekly monsoon mode, directly wind‐forced surface currents carry river water away to the east and north, leading to increased salinity at the moorings, and rise of sea level by 0.1–0.5 m along the eastern and northern boundary of the bay. During July–August 2015, a shallow pool of low‐salinity river water lies in the northeastern bay. The amplitude of a 20‐day oscillation of sea surface temperature (SST) is two times larger within the fresh pool than in the saltier ocean to the west, although surface heat flux is nearly identical in the two regions. This is direct evidence that spatial‐temporal variations of BoB salinity influences sub‐seasonal SST variations, and possibly SST‐mediated monsoon air‐sea interaction.The authors thank the Ministry of Earth Sciences (MoES) institutes NIOT and INCOIS, and the Upper Ocean Processes (UOP) group at WHOI for design, integration, and deployment of moorings in the BoB. The WHOI mooring was deployed from the ORV Sagar Nidhi and recovered from the ORV Sagar Kanya—we thank the officers, crew and science teams on the cruises for their support. Sengupta, Ravichandran and Sukhatme acknowledge MoES and the National Monsoon Mission, Indian Institute of Tropical Meteorology (IITM), Pune, for support; Lucas and Farrar acknowledge the US Office of Naval Research for support of ASIRI through grants N00014‐13‐1‐0489, N0001413‐100453, N0001417‐12880. We thank S. Shivaprasad, Dipanjan Chaudhuri and Jared Buckley for discussion on ocean currents and Ekman flow, and Fabien Durand for discussion on sea level. JSL would like to thank the Divecha Center for Climate Change, IISc., for support. DS acknowledges support from the Department of Science and Technology (DST), New Delhi, under the Indo‐Spanish Programme.2021-05-1

Nucleus Accumbens Adenosine A2A Receptors Regulate Exertion of Effort by Acting on the Ventral Striatopallidal Pathway

Goal-directed actions are sensitive to work-related response costs, and dopamine in nucleus accumbens is thought to modulate the exertion of effort in motivated behavior. Dopamine-rich striatal areas such as nucleus accumbens also contain high numbers of adenosine A2A receptors, and, for that reason, the behavioral and neurochemical effects of the adenosine A2A receptor agonist CGS 21680 [2-p-(2-carboxyethyl) phenethylamino-5′-N-ethylcarboxamidoadenosine] were investigated. Stimulation of accumbens adenosine A2A receptors disrupted performance of an instrumental task with high work demands (i.e., an interval lever-pressing schedule with a ratio requirement attached) but had little effect on a task with a lower work requirement. Immunohistochemical studies revealed that accumbens neurons that project to the ventral pallidum showed adenosine A2A receptors immunoreactivity. Moreover, activation of accumbens A2A receptors by local injections of CGS 21680 increased extracellular GABA levels in the ventral pallidum. Combined contralateral injections of CGS 21680 into the accumbens and the GABAA agonist muscimol into ventral pallidum (i.e., “disconnection” methods) also impaired response output, indicating that these structures are part of a common neural circuitry regulating the exertion of effort. Thus, accumbens adenosine A2A receptors appear to regulate behavioral activation and effort-related processes by modulating the activity of the ventral striatopallidal pathway. Research on the effort-related functions of these forebrain systems may lead to a greater understanding of pathological features of motivation, such as psychomotor slowing, anergia, and fatigue in depression

Dopamine/adenosine interactions related to locomotion and tremor in animal models: Possible relevance to parkinsonism

Abstract Adenosine A 2A antagonists can exert antiparkinsonian effects in animal models. Recent experiments studied the ability of MSX-3 (an adenosine A 2A antagonist) to reverse the locomotor suppression and tremor produced by dopamine antagonists in rats. MSX-3 reversed haloperidolinduced suppression of locomotion, and reduced the tremulous jaw movements induced by haloperidol, pimozide, and reserpine. Infusions of MSX-3 into the nucleus accumbens core increased locomotion in haloperidol-treated rats, but there were no effects of infusions into the accumbens shell or ventrolateral neostriatum. In contrast, MSX-3 injected into the ventrolateral neostriatum reduced pimozide-induced tremulous jaw movements. Dopamine/adenosine interactions in different striatal subregions are involved in distinct aspects of motor function

Managing cow's milk protein allergy during the 2022 formula shortage: decision-making among pediatric healthcare providers

IntroductionCow's milk protein allergy (CMPA) affects 2%-7% of infants and is managed with hypoallergenic formulas. The 2022 recalls of infant formulas due to factors including contamination led to specialty formula shortages, highlighting CMPA management challenges. Understanding healthcare providers' (HCPs) decision-making in transitioning to alternative formulas during shortages is crucial. Limited attention has been given to how pediatric physicians make these choices.MethodsThis study utilized US HCPs' de-identified survey data to assess driving factors when switching extensively hydrolyzed formulas during shortages.Results104 eligible HCPs participated, including general pediatrics, pediatric allergy/immunology, and pediatric gastroenterology specialists. Safety, tolerability, and efficacy were identified as top factors for switching formulas. Formula 1 was considered well-tolerated, patient-accepted, and safe by all HCPs. Most expressed strong belief in Formula 1's safety and effectiveness.DiscussionFindings inform CMPA management during shortages, offering guidance to HCPs for suitable formula selection and enhanced infant care