Effects of High-Intensity Interval Training Protocols on Liver Enzymes and Wellness in Women.

BACKGROUND: Single-modality, high-intensity interval training (HIIT) using traditional cardiorespiratory exercise selection has been found to provide similar and sometimes superior cardiometabolic effects compared with moderate-intensity continuous training. However, little is known regarding the cardiometabolic and psychosocial effects of HIIT using resistance training modalities. Therefore, this study aims to compare the effects of HIIT using rowing (R-HIIT) and multimodal HIIT (MM-HIIT) using resistance training on liver enzymes, cardiometabolic risk factors, and psychosocial outcomes. METHOD: Recreationally active females with a body mass index <30 kg/m2 (N = 16, 23.0 ± 5.9 years) were randomized into a MM-HIIT or R-HIIT group and completed a 12-week HIIT intervention (ClinicalTrials.gov registration number: https://clinicaltrials.gov/ct2/show/NCT03093441) using principles of social cognitive theory (SCT). Participants completed pre- and postintervention measurements on anthropometrics, resting heart rate, blood pressure, blood measures (lipids, liver enzymes, and glucose), exercise self-efficacy, and perceived wellness. Analysis of covariance was used to examine differences in postintervention measures between groups after controlling for baseline values, waist circumference, and waist-to-height ratio. RESULTS: R-HIIT group had significantly decreased alanine aminotransferase (mean difference = 13.16, P=0.013, effect size (ES) = 0.44, confidence interval (CI) = 3.40 to 22.92) and aspartate aminotransferase (mean difference = 10.79, P=0.024, ES = 0.38, CI = 1.67 to 19.90) levels compared with the M-HIIT group, and the whole group had improved wellness scores (14.72 ± 2.6 to 16.89 ± 2.76, P=0.002). CONCLUSION: R-HIIT may be an effective preventative method for improving liver health in females without obesity. When using principles of SCT, HIIT may enhance overall well-being.

Population collapse dynamics in Acropora downingi, an Arabian/Persian Gulf ecosystem-engineering coral, linked to rising temperature.

As in the tropical Atlantic, Acropora populations in the southern Persian/Arabian Gulf plummeted within two decades after having been ecosystem engineers on most wave-exposed reefs since the Pleistocene. Since 1996/1998 live coral cover in the Gulf declined by over 90% in many areas, primarily due to bleaching and diseases caused by rising temperatures. In the formerly dominant table-coral species A. downingi, population dynamics corresponding to disturbance regimes was quantified in three transition matrices (lower disturbance pre-1996; moderate disturbance from 1998 to 2010 and 2013 to 2017, disturbed in 1996/1998, 2010/11/12, 2017). Increased disturbance frequency and severity caused progressive reduction in coral size, cover, and population fecundity. Small size-classes were bolstered more by partial colony mortality than sexual recruitment. Some large corals had a size refuge and resisted die-back but were also lost with increasing disturbance. Matrix and biophysical larval flow models suggested one metapopulation. Southern, Arabian, populations could be connected to northern, Iranian, populations but this connectivity was lost under assumptions of pelagic larval duration at rising temperatures shortened to a third. Then, the metapopulation disintegrated into isolated populations. Connectivity required to avoid extinctions increased exponentially with disturbance frequency and correlation of disturbances across the metapopulation. Populations became unsustainable at eight disturbances in 15 years, when even highest theoretical recruitment no longer compensated mortality. This lethal disturbance frequency was 3-fold that of the moderately disturbed monitoring period and 4-fold of the preceding low-disturbance period-suggesting ongoing shortening of the disturbance-free period. Observed population collapse and environmental changes in the Gulf suggest that A. downingi is heading toward at least functional extinction mainly due to increasingly frequent temperature-induced mortality events, clearly linked to climate change.

The Impact of Different High-Intensity Interval Training Protocols on Body Composition and Physical Fitness in Healthy Young Adult Females.

Although traditional high-intensity interval training (HIIT) has been effective in improving body composition and physical fitness, it is unclear how multimodal HIIT affects these variables. This study compared the differences between these two training programs on body composition and physical fitness in apparently healthy, nonobese young adult females. A total of 16 participants (mean age = 23 ± 5.08 years) completed a 12-week HIIT intervention with two treatment groups: rowing and multimodal. Immediately before and after the intervention, the following measures were assessed: body mass index (BMI), total body mass, waist circumference, waist-to-height ratio, total body fat %, visceral adipose tissue, lean mass, bone mineral outcomes, cardiovascular fitness, and muscular fitness. A general linear model with repeated measures was used to assess changes over time for the group as a whole, as well as between-group differences. For the group as a whole, there were significant decrease in total body fat % (p = 0.04) and significant increases in BMI (p = 0.015), total body mass (p = 0.003), lean mass (p < 0.001), bone mineral content (BMC) (p < 0.001), VO2max (p = 0.01), broad jump (p = 0.001), squat endurance (p = 0.006), press (p < 0.001), back squat (p < 0.001), and deadlift (p < 0.001) one repetition maximum (1RM). The multimodal group (p < 0.001) increased deadlift 1RM significantly more than the rowing group (p = 0.002). HIIT can be an effective means for improving cardiovascular and muscular fitness, increasing lean mass and BMC, and thereby improving cardiometabolic as well as musculoskeletal health in nonobese females. Using a multimodal approach may give the added benefit of superior muscular strength increases.

Transforming management of tropical coastal seas to cope with challenges of the 21st century.

Over 1.3 billion people live on tropical coasts, primarily in developing countries. Many depend on adjacent coastal seas for food, and livelihoods. We show how trends in demography and in several local and global anthropogenic stressors are progressively degrading capacity of coastal waters to sustain these people. Far more effective approaches to environmental management are needed if the loss in provision of ecosystem goods and services is to be stemmed. We propose expanded use of marine spatial planning as a framework for more effective, pragmatic management based on ocean zones to accommodate conflicting uses. This would force the holistic, regional-scale reconciliation of food security, livelihoods, and conservation that is needed. Transforming how countries manage coastal resources will require major change in policy and politics, implemented with sufficient flexibility to accommodate societal variations. Achieving this change is a major challenge - one that affects the lives of one fifth of humanity.

One size does not fit all: the emerging frontier in large-scale marine conservation.

On the 20th anniversary of the Convention on Biological Diversity, a network of very large marine protected areas (the Big Ocean network) has emerged as a key strategy in the move to arrest marine decline and conserve some of the last remaining relatively undisturbed marine areas on the globe. Here we outline the ecological, economic and policy benefits of very large-scale MPAs and show their disproportionate value to global marine conservation targets. In particular we point out that very large-scale MPAs are a critical component of reaching the Aichi targets of protecting 10% of global marine habitats by 2020, because in addition to encompassing entire ecosystems, they will bring forward the expected date of achievement by nearly three decades (2025 as opposed to 2054). While the need for small MPAs remains critical, large MPAs will complement and enhance these conservation efforts. Big Ocean sites currently contain more than 80% of managed area in the sea, and provide our best hope for arresting the global decline in marine biodiversity.

Climate change impacts on coral reefs: synergies with local effects, possibilities for acclimation, and management implications.

Most reviews concerning the impact of climate change on coral reefs discuss independent effects of warming or ocean acidification. However, the interactions between these, and between these and direct local stressors are less well addressed. This review underlines that coral bleaching, acidification, and diseases are expected to interact synergistically, and will negatively influence survival, growth, reproduction, larval development, settlement, and post-settlement development of corals. Interactions with local stress factors such as pollution, sedimentation, and overfishing are further expected to compound effects of climate change. Reduced coral cover and species composition following coral bleaching events affect coral reef fish community structure, with variable outcomes depending on their habitat dependence and trophic specialisation. Ocean acidification itself impacts fish mainly indirectly through disruption of predation- and habitat-associated behavior changes. Zooxanthellate octocorals on reefs are often overlooked but are substantial occupiers of space; these also are highly susceptible to bleaching but because they tend to be more heterotrophic, climate change impacts mainly manifest in terms of changes in species composition and population structure. Non-calcifying macroalgae are expected to respond positively to ocean acidification and promote microbe-induced coral mortality via the release of dissolved compounds, thus intensifying phase-shifts from coral to macroalgal domination. Adaptation of corals to these consequences of CO2 rise through increased tolerance of corals and successful mutualistic associations between corals and zooxanthellae is likely to be insufficient to match the rate and frequency of the projected changes. Impacts are interactive and magnified, and because there is a limited capacity for corals to adapt to climate change, global targets of carbon emission reductions are insufficient for coral reefs, so lower targets should be pursued. Alleviation of most local stress factors such as nutrient discharges, sedimentation, and overfishing is also imperative if sufficient overall resilience of reefs to climate change is to be achieved.

Human impact on atolls leads to coral loss and community homogenisation: a modeling study.

We explore impacts on pristine atolls subjected to anthropogenic near-field (human habitation) and far-field (climate and environmental change) pressure. Using literature data of human impacts on reefs, we parameterize forecast models to evaluate trajectories in coral cover under impact scenarios that primarily act via recruitment and increased mortality of larger corals. From surveys across the Chagos, we investigate the regeneration dynamics of coral populations distant from human habitation after natural disturbances. Using a size-based mathematical model based on a time-series of coral community and population data from 1999-2006, we provide hind- and forecast data for coral population dynamics within lagoons and on ocean-facing reefs verified against monitoring from 1979-2009. Environmental data (currents, temperatures) were used for calibration. The coral community was simplified into growth typologies: branching and encrusting, arboresent and massive corals. Community patterns observed in the field were influenced by bleaching-related mortality, most notably in 1998. Survival had been highest in deep lagoonal settings, which suggests a refuge. Recruitment levels were higher in lagoons than on ocean-facing reefs. When adding stress by direct human pressure, climate and environmental change as increased disturbance frequency and modified recruitment and mortality levels (due to eutrophication, overfishing, pollution, heat, acidification, etc), models suggest steep declines in coral populations and loss of community diversification among habitats. We found it likely that degradation of lagoonal coral populations would impact regeneration potential of all coral populations, also on ocean-facing reefs, thus decreasing reef resilience on the entire atoll.

Diversity and distribution of symbiodinium associated with seven common coral species in the Chagos Archipelago, central Indian Ocean.

The Chagos Archipelago designated as a no-take marine protected area in 2010, lying about 500 km south of the Maldives in the Indian Ocean, has a high conservation priority, particularly because of its fast recovery from the ocean-wide massive coral mortality following the 1998 coral bleaching event. The aims of this study were to examine Symbiodinium diversity and distribution associated with scleractinian corals in five atolls of the Chagos Archipelago, spread over 10,000 km(2). Symbiodinium clade diversity in 262 samples of seven common coral species, Acropora muricata, Isopora palifera, Pocillopora damicornis, P. verrucosa, P. eydouxi, Seriatopora hystrix, and Stylophora pistillata were determined using PCR-SSCP of the ribosomal internal transcribed spacer 1 (ITS1), PCR-DDGE of ITS2, and phylogenetic analyses. The results indicated that Symbiodinium in clade C were the dominant symbiont group in the seven coral species. Our analysis revealed types of Symbiodinium clade C specific to coral species. Types C1 and C3 (with C3z and C3i variants) were dominant in Acroporidae and C1 and C1c were the dominant types in Pocilloporidae. We also found 2 novel ITS2 types in S. hystrix and 1 novel ITS2 type of Symbiodinium in A. muricata. Some colonies of A. muricata and I. palifera were also associated with Symbiodinium A1. These results suggest that corals in the Chagos Archipelago host different assemblages of Symbiodinium types then their conspecifics from other locations in the Indian Ocean; and that future research will show whether these patterns in Symbiodinium genotypes may be due to local adaptation to specific conditions in the Chagos.

Transcutaneous immunization with a Vibrio cholerae O1 Ogawa synthetic hexasaccharide conjugate following oral whole-cell cholera vaccination boosts vibriocidal responses and induces protective immunity in mice.

A shortcoming of currently available oral cholera vaccines is their induction of relatively short-term protection against cholera compared to that afforded by wild-type disease. We were interested in whether transcutaneous or subcutaneous boosting using a neoglycoconjugate vaccine made from a synthetic terminal hexasaccharide of the O-specific polysaccharide of Vibrio cholerae O1 (Ogawa) coupled to bovine serum albumin as a carrier (CHO-BSA) could boost lipopolysaccharide (LPS)-specific and vibriocidal antibody responses and result in protective immunity following oral priming immunization with whole-cell cholera vaccine. We found that boosting with CHO-BSA with immunoadjuvantative cholera toxin (CT) or Escherichia coli heat-labile toxin (LT) following oral priming with attenuated V. cholerae O1 vaccine strain O395-NT resulted in significant increases in serum anti-V. cholerae LPS IgG, IgM, and IgA (P < 0.01) responses as well as in anti-Ogawa (P < 0.01) and anti-Inaba (P < 0.05) vibriocidal titers in mice. The LPS-specific IgA responses in stool were induced by transcutaneous (P < 0.01) but not subcutaneous immunization. Immune responses following use of CT or LT as an adjuvant were comparable. In a neonatal mouse challenge assay, immune serum from boosted mice was associated with 79% protective efficacy against death. Our results suggest that transcutaneous and subcutaneous boosting with a neoglycoconjugate following oral cholera vaccination may be an effective strategy to prolong protective immune responses against V. cholerae.

Stability Ball Sitting versus Chair Sitting During Sub-maximal Arm Ergometry.

It was predicted that sitting on a stability ball during arm ergometry would elevate cardiovascular parameters when compared to sitting on a chair and that this would be associated with greater recruitment of trunk and leg skeletal muscles. METHODS: Open-circuit spirometry, videotaping, blood pressure, heart rate, and EMG were conducted during rest and four minute stages of 15 W, 30 W, and 45 W using a Monark arm ergometer. Twenty-six apparently healthy adults exercised twice, once sitting on a stability ball and the other sitting on a chair (order randomized), with 45 to 60 minutes of rest between. ANOVA for repeated measures and paired-t testing were used for analysis. RESULTS: Oxygen consumption was significantly 10 to 16% higher during exercise while sitting on the stability ball. There were no significant differences between sitting modes for heart rate, SBP, and DBP. Also, resting and exercise rectus femoris and 45 W external oblique EMGs were significantly higher on the stability ball. Finally, the knee was significantly more extended with the feet farther apart and more forward on the stability ball. CONCLUSION: The stability ball significantly elevates oxygen consumption during sub-maximal arm cranking without significantly increasing heart rate or blood pressure and this is associated with increased thigh muscle activation and lower leg repositioning.

Stability Ball Sitting Elevates Peak Arm Ergometry Oxygen Consumption and Heart Rate.

This study compared sitting on a stability ball (B) to sitting on a chair (C) during arm ergometry to determine the impact on peak VO2, peak heart rate (HR), and exercise intensity prescription. Open-circuit spirometer, blood pressure, and HR were monitored during rest and continuous graded exercise test to exhaustion using an arm ergometer. Twenty-seven apparently healthy adults exercised twice, once at B and the other trial C (order randomized), with 60 minutes of rest between trials. ANOVA for repeated measures (α < 0.05) and paired t testing using Holm's-sequential Bonferroni were used to analyze results for 30 W, 45 W, Penultimate, and Peak stages of exercise. VO2 was significantly higher (8% to 12%, P < 0.001) for all stages of exercise for B compared to C. HR was significantly higher (P < 0.001) only at the Penultimate and Peak levels (3% and 2%, respectively) for B compared to C; all other sub-maximal HRs were not significantly different. There were no significant main effects or interactions (P≥ 0.138) when VO2 and HR were expressed as percentage of maximum. Compared to chair sitting, the stability ball has a greater absolute metabolic response with little impact on HR. Prescribing exercise with absolute MET levels should consider this; however, intensity as a percentage of maximum may not be affected by the stability ball.

Climate warming, marine protected areas and the ocean-scale integrity of coral reef ecosystems.

Coral reefs have emerged as one of the ecosystems most vulnerable to climate variation and change. While the contribution of a warming climate to the loss of live coral cover has been well documented across large spatial and temporal scales, the associated effects on fish have not. Here, we respond to recent and repeated calls to assess the importance of local management in conserving coral reefs in the context of global climate change. Such information is important, as coral reef fish assemblages are the most species dense vertebrate communities on earth, contributing critical ecosystem functions and providing crucial ecosystem services to human societies in tropical countries. Our assessment of the impacts of the 1998 mass bleaching event on coral cover, reef structural complexity, and reef associated fishes spans 7 countries, 66 sites and 26 degrees of latitude in the Indian Ocean. Using Bayesian meta-analysis we show that changes in the size structure, diversity and trophic composition of the reef fish community have followed coral declines. Although the ocean scale integrity of these coral reef ecosystems has been lost, it is positive to see the effects are spatially variable at multiple scales, with impacts and vulnerability affected by geography but not management regime. Existing no-take marine protected areas still support high biomass of fish, however they had no positive affect on the ecosystem response to large-scale disturbance. This suggests a need for future conservation and management efforts to identify and protect regional refugia, which should be integrated into existing management frameworks and combined with policies to improve system-wide resilience to climate variation and change.

Effect of a blueberry nutritional supplement on macronutrients, food group intake, and plasma vitamin E and vitamin C in US athletes.

Antioxidants from a blueberry beverage may impact plasma vitamins. We examined vitamins/food selection in 12 college athletes during 30 days compared with placebo. Blood was collected before and after exercise at the beginning of the study (day 1) and then after a 30-day period of taking a daily supplemental beverage (day 30). The six trials involved blood that was drawn pre-beverage ingestion/pre-exercise (trials 1 and 4), post-beverage ingestion/pre-exercise (trials 2 and 5), and post-beverage ingestion/1 h post-exercise (trials 3 and 6), on day 1 (trials 1, 2, and 3) and day 30 (trials 4, 5, and 6). Analysis of variance revealed non-significant differences for macronutrient or gamma-tocopherol and vitamin C intakes by food frequency questionnaire or plasma vitamins by liquid chromatography. There was a trend (P = 0.083) in the group x time interaction for alpha-tocopherol intake by repeated-measures analysis of variance. Blueberry alpha-tocopherol (23.91 +/- 9.31 mg) was significantly (P < 0.05) higher than placebo alpha-tocopherol intake (7.59 +/- 0.95 mg) on day 1, but not on day 30 (blueberry, alpha-tocopherol = 9.04 +/- 2.35 mg, placebo, alpha-tocopherol = 11.46 +/- 3.65 mg) by pairwise comparisons. Blueberry supplementation did not affect plasma vitamin concentrations or gamma-tocopherol and vitamin C intakes, and may reduce alpha-tocopherol intake in those starting with a higher alpha-tocopherol intake, yet not altering athletes' eating habits.

Lactate levels in severe malarial anaemia are associated with haemozoin-containing neutrophils and low levels of IL-12.

BACKGROUND: Hyperlactataemia is often associated with a poor outcome in severe malaria in African children. To unravel the complex pathophysiology of this condition the relationship between plasma lactate levels, parasite density, pro- and anti-inflammatory cytokines, and haemozoin-containing leucocytes was studied in children with severe falciparum malarial anaemia. METHODS: Twenty-six children with a primary diagnosis of severe malarial anaemia with any asexual Plasmodium falciparum parasite density and Hb < 5 g/dL were studied and the association of plasma lactate levels and haemozoin-containing leucocytes, parasite density, pro- and anti-inflammatory cytokines was measured. The same associations were measured in non-severe malaria controls (N = 60). RESULTS: Parasite density was associated with lactate levels on admission (r = 0.56, P < 0.005). Moreover, haemozoin-containing neutrophils and IL-12 were strongly associated with plasma lactate levels, independently of parasite density (r = 0.60, P = 0.003 and r = -0.46, P = 0.02, respectively). These associations were not found in controls with uncomplicated malarial anaemia. CONCLUSION: These data suggest that blood stage parasites, haemozoin and low levels of IL-12 may be associated with the development of hyperlactataemia in severe malarial anaemia.

Characterization of melanophore morphology by fractal dimension analysis.

Fractal or focal dimension (FD) analysis is a valuable tool to identify physiologic stimuli at the cellular and tissue levels that allows for quantification of cell perimeter complexity. The FD analysis was determined on fluorescence images of caffeine- or epinephrine-treated (or untreated control) killifish Fundulus heteroclitus (Linneaus) melanophores in culture. Cell perimeters were indicated by rhodamine-phalloidin labeling of cortical microfilaments using box-counting FD analysis. Caffeine-treated melanophores displayed dispersed melanosomes in cells with less serrated edges and reduced FD and complexity. Complexity in epinephrine-treated cells was significantly higher than the caffeine-treated cells or in the control. Cytoarchitectural variability of the cell perimeter is expected because cells change shape when cued with agents. Epinephrine-treated melanophores demonstrated aggregated melanosomes in cells with more serrated edges, significantly higher FD and thus complexity. Melanophores not treated with caffeine or epinephrine produced variable distributions of melanosomes and resulted in cells with variably serrated edges and intermediate FD with a larger SE of the regression and greater range of complexity. Dispersion of melanosomes occurs with rearrangements of the cytoskeleton to accommodate centrifugal distribution of melanosomes throughout the cell and to the periphery. The loading of melanosomes onto cortical microfilaments may provide a less complex cell contour, with the even distribution of the cytoskeleton and melanosomes. Aggregation of melanosomes occurs with rearrangements of the cytoskeleton to accommodate centripetal distribution of melanosomes. The aggregation of melanosomes may contribute to centripetal retraction of the cytoskeleton and plasma membrane. The FD analysis is, therefore, a convenient method to measure contrasting morphologic changes within stimulated cells.

Predicted recurrences of mass coral mortality in the Indian Ocean.

In 1998, more than 90% of shallow corals were killed on most Indian Ocean reefs. High sea surface temperature (SST) was a primary cause, acting directly or by interacting with other factors. Mean SSTs have been forecast to rise above the 1998 values in a few decades; however, forecast SSTs rarely flow seamlessly from historical data, or may show erroneous seasonal oscillations, precluding an accurate prediction of when lethal SSTs will recur. Differential acclimation by corals in different places complicates this further. Here I scale forecast SSTs at 33 Indian Ocean sites where most shallow corals died in 1998 (ref. 1) to identify geographical patterns in the timing of probable repeat occurrences. Reefs located 10-15 degrees south will be affected every 5 years by 2010-2025. North and south from this, dates recede in a pattern not directly related to present SSTs; paradoxically, some of the warmest sites may be affected last. Temperatures lethal to corals vary in this region by 6 degrees C, and acclimation of a modest 2 degrees C by corals could prolong their survival by nearly 100 years.

Differential effects of exercise training in men and women with chronic heart failure.

BACKGROUND: Abnormalities of myosin heavy chain (MHC) isoforms, enzyme activity, and capillarity contribute to the exercise intolerance that is characteristic of patients with heart failure. To what extent these changes can be reversed with exercise training and whether differences exist in the responses of men and women remains uncertain. We described and compared the effects of exercise training on exercise capacity and skeletal muscle histochemistry in men and women with chronic heart failure. METHODS: Fifteen patients (10 male) undergoing standard medical therapy completed a 14- to 24-week exercise training program. Peak oxygen consumption, MHC isoforms, capillary density, and selected metabolic enzymes were assessed before and after training. RESULTS: Peak oxygen consumption was improved 14% (P <.05); however, this increase was mostly because of the improvement observed in men versus women (+20% versus +2%, respectively, P <.01). At baseline, MHC I content was lower in men than in women (33% +/- 3% vs 49.6% +/- 5.5%, P <.05). MHC I improved with training in men, to 45.6% +/- 4.5% (+38%, P <.05), versus women (-3%, P =.82), and the increase in men tended (P =.12) to be significant when compared with that in women. There were no significant changes in capillary density or muscle enzyme activity with training in the group as a whole or in men and women separately. CONCLUSION: Among patients with chronic heart failure, improvements in peak exercise capacity may be more pronounced in men than in women. This difference in response of functional capacity to training paralleled differences observed between men and women for changes in MHC I isoforms.

Erosion vs. recovery of coral reefs after 1998 El Niño: Chagos reefs, Indian Ocean.

Three years after most corals died on the central Indian Ocean reefs of Chagos, erosion and recovery were studied to 30 m depth. Mortality was near-total to 15 m deep in northern atolls, and to > 35 m in central and southern atolls. Some reef surfaces have 'dropped' 1.5 m due to the loss of dense coral thickets. Coral bioerosion is substantial, reducing 3-D reef 'structure' and forming unconsolidated rubble. Juvenile corals are abundant, though mostly on eroding or unstable substrates, and are of less robust species. Reef fish abundance and diversity at 15 m depth remains high; species dependent on corals have diminished, while some herbivores and detritivores have increased. A new sea surface temperature (SST) data set shows that mean SST has risen 0.65 degree C since 1950. The critical SST causing the mortality in Chagos was 29.9 degrees C.

Cloned delta-opioid receptors in GH(3) cells inhibit spontaneous Ca(2+) oscillations and prolactin release through K(IR) channel activation.

Opioid receptors can couple to K(+) and Ca(2+) channels, adenylyl cyclase, and phosphatidyl inositol turnover. Any of these actions may be important in the regulation of neurotransmitter and hormone release from excitable cells. GH(3) cells exhibit spontaneous oscillations of intracellular Ca(2+) concentration ([Ca(2+)](i)) and prolactin release. Activation of cloned delta-opioid receptors stably expressed in GH(3) cells inhibits both spontaneous Ca(2+) signaling and basal prolactin release. The objective of this study was to examine a possible role for K(+) channels in these processes using the patch-clamp technique, fluorescence imaging, and a sensitive ELISA for prolactin. The selective delta receptor agonist [D-Pen(2), D-Pen(2)]enkephalin (DPDPE) inhibited [Ca(2+)](i) oscillations in GH(3) cells expressing both mu and delta receptors (GH(3)MORDOR cells) but had no effect on control GH(3) cells or cells expressing mu receptors alone (GH(3)MOR cells). The inhibition of [Ca(2+)](i) oscillations by DPDPE was unaffected by thapsigargin pretreatment, suggesting that this effect is independent of inositol 1,4,5-triphosphate-sensitive Ca(2+) stores. DPDPE caused a concentration-dependent inhibition of prolactin release from GH(3)MORDOR cells with an IC(50) of 4 nM. DPDPE increased inward K(+) current recorded from GH(3)MORDOR cells but had no significant effect on K(+) currents recorded from control GH(3) cells or GH(3)MOR cells. The mu receptor agonist morphine also had no effect on currents recorded from control cells but activated inward K(+) currents recorded from GH(3)MOR and GH(3)MORDOR cells. Somatostatin activated inward currents recorded from all three cell lines. The DPDPE-sensitive K(+) current was inwardly rectifying and was inhibited by Ba(2+) but not TEA. DPDPE had no effect on delayed rectifier-, Ca(2+)-, and voltage-activated or A-type K(+) currents, recorded from GH(3)MORDOR cells. Ba(2+) attenuated the inhibition of [Ca(2+)](i) and prolactin release by DPDPE, whereas TEA had no effect, consistent with an involvement of K(IR) channels in these actions of the opioid.

Effects of social defeat and of diazepam on behavior in a resident-intruder test in male DBA/2 mice.

Social stress induces robust behavioral and physiological changes, some of which may alter the responsiveness to pharmacological agents, including diazepam (DZP). We used a resident-intruder paradigm to (1) develop a comprehensive ethogram of behavioral changes following social defeat (SD) in the socially reactive strain, DBA/2 male mice, (2) determine whether acute exposure of DBA/2 mice to low-dose DZP would induce flight or aggressive behavior, both of which have been observed in other rodent models and (3) to test whether prior social stress affects responses to DZP. Behavioral responses to a nonaggressive intruder (NAI) mouse 24 h post-SD were measured in resident subject mice exposed to DZP (0, 0.5, 2.0 mg/kg, ip) either prior to the resident-intruder test (Experiment 1) or immediately post-SD (Experiment 2); control mice were not defeated (NOSD). In general, SD mice displayed increased passive and active avoidance, defense, immobility, and risk assessment relative to NOSD mice. In Experiment 1, mice treated acutely with 0.5 mg/kg DZP had more approach and flight behavior, while those treated with 2.0 mg/kg DZP had more avoidance than vehicle-treated mice, independent of SD. In Experiment 2, acute DZP (2 mg/kg) induced effects 24 h later, possibly secondary to withdrawal. In a nonsocial context (Experiment 3), DZP increased exploratory activity.