Drug Predictive Cues Activate Aversion-Sensitive Striatal Neurons That Encode Drug Seeking

Drug-associated cues have profound effects on an addict’s emotional state and drug-seeking behavior. Although this influence must involve the motivational neural system that initiates and encodes the drug-seeking act, surprisingly little is known about the nature of such physiological events and their motivational consequences. Three experiments investigated the effect of a cocaine-predictive stimulus on dopamine signaling, neuronal activity, and reinstatement of cocaine seeking. In all experiments, rats were divided into two groups (paired and unpaired), and trained to self-administer cocaine in the presence of a tone that signaled the immediate availability of the drug. For rats in the paired group, self-administration sessions were preceded by a taste cue that signaled delayed drug availability. Assessments of hedonic responses indicated that this delay cue became aversive during training. Both the self-administration behavior and the immediate cue were subsequently extinguished in the absence of cocaine. After extinction of self-administration behavior, the presentation of the aversive delay cue reinstated drug seeking. In vivo electrophysiology and voltammetry recordings in the nucleus accumbens measured the neural responses to both the delay and immediate drug cues after extinction. Interestingly, the presentation of the delay cue simultaneously decreased dopamine signaling and increased excitatory encoding of the immediate cue. Most importantly, the delay cue selectively enhanced the baseline activity of neurons that would later encode drug seeking. Together these observations reveal how cocaine cues can modulate not only affective state, but also the neurochemical and downstream neurophysiological environment of striatal circuits in a manner that promotes drug seeking

Aversive Stimuli Drive Drug Seeking in a State of Low Dopamine Tone

Background Stressors negatively impact emotional state and drive drug seeking, in part, by modulating the activity of the mesolimbic dopamine system. Unfortunately, the rapid regulation of dopamine signaling by the aversive stimuli that cause drug seeking is not well characterized. In a series of experiments, we scrutinized the subsecond regulation of dopamine signaling by the aversive stimulus, quinine, and tested its ability to cause cocaine seeking. Additionally, we examined the midbrain regulation of both dopamine signaling and cocaine seeking by the stress-sensitive peptide, corticotropin releasing factor (CRF). Methods Combining fast-scan cyclic voltammetry with behavioral pharmacology, we examined the effect of intraoral quinine administration on nucleus accumbens dopamine signaling and hedonic expression in 21 male Sprague-Dawley rats. We tested the role of CRF in modulating aversion-induced changes in dopamine concentration and cocaine seeking by bilaterally infusing the CRF antagonist, CP-376395, into the ventral tegmental area (VTA). Results We found that quinine rapidly reduced dopamine signaling on two distinct time scales. We determined that CRF acted in the VTA to mediate this reduction on only one of these time scales. Further, we found that the reduction of dopamine tone and quinine-induced cocaine seeking were eliminated by blocking the actions of CRF in the VTA during the experience of the aversive stimulus. Conclusions These data demonstrate that stress-induced drug seeking can occur in a terminal environment of low dopamine tone that is dependent on a CRF-induced decrease in midbrain dopamine activity

Effect of Whole Body Vibration on Delayed-onset Muscle Soreness

The purpose of this study was to examine the effects of whole body vibration (WBV) on delayed-onset muscle soreness, specifically pain ratings, sit-and-reach scores, and vertical jump scores. Participants in the study were 20 (10 male; 10 female) healthy, college-aged students (20.85 1.81 years). All students completed an IRB informed consent document and health history questionnaire to determine eligibility. Participants were randomly assigned to a treatment or control group. For each participant, delayed-onset muscle soreness was induced via weighted lunges. Subsequently, the experimental treatment group underwent 10min. WBV before and after assessment for five consecutive days while the control group walked on a treadmill before and after each assessment. Assessment included visual analog pain rating, flexibility, and vertical jump measures. No significant results were found between the control and experimental groups regarding pain ratings, sit-and-reach scores, and vertical jump scores. While not statiSchool of Teaching and Curriculum Leadershi

Corticosterone Regulates Both Naturally Occurring and Cocaine‐Induced Dopamine Signaling by Selectively Decreasing Dopamine Uptake

Stressful and aversive events promote maladaptive reward‐seeking behaviors such as drug addiction by acting, in part, on the mesolimbic dopamine system. Using animal models, data from our laboratory and others show that stress and cocaine can interact to produce a synergistic effect on reward circuitry. This effect is also observed when the stress hormone corticosterone is administered directly into the nucleus accumbens (NAc), indicating that glucocorticoids act locally in dopamine terminal regions to enhance cocaine\u27s effects on dopamine signaling. However, prior studies in behaving animals have not provided mechanistic insight. Using fast‐scan cyclic voltammetry, we examined the effect of systemic corticosterone on spontaneous dopamine release events (transients) in the NAc core and shell in behaving rats. A physiologically relevant systemic injection of corticosterone (2 mg/kg i.p.) induced an increase in dopamine transient amplitude and duration (both voltammetric measures sensitive to decreases in dopamine clearance), but had no effect on the frequency of transient release events. This effect was compounded by cocaine (2.5 mg/kg i.p.). However, a second experiment indicated that the same injection of corticosterone had no detectable effect on the dopaminergic encoding of a palatable natural reward (saccharin). Taken together, these results suggest that corticosterone interferes with naturally occurring dopamine uptake locally, and this effect is a critical determinant of dopamine concentration specifically in situations in which the dopamine transporter is pharmacologically blocked by cocaine

Corticosterone Acts in the Nucleus Accumbens to Enhance Dopamine Signaling and Potentiate Reinstatement of Cocaine Seeking

Stressful life events are important contributors to relapse in recovering cocaine addicts, but the mechanisms by which they influence motivational systems are poorly understood. Studies suggest that stress may “set the stage” for relapse by increasing the sensitivity of brain reward circuits to drug-associated stimuli. We examined the effects of stress and corticosterone on behavioral and neurochemical responses of rats to a cocaine prime after cocaine self-administration and extinction. Exposure of rats to acute electric footshock stress did not by itself reinstate drug-seeking behavior but potentiated reinstatement in response to a subthreshold dose of cocaine. This effect of stress was not observed in adrenalectomized animals, and was reproduced in nonstressed animals by administration of corticosterone at a dose that reproduced stress-induced plasma levels. Pretreatment with the glucocorticoid receptor antagonist RU38486 did not block the corticosterone effect. Corticosterone potentiated cocaine-induced increases in extracellular dopamine in the nucleus accumbens (NAc), and pharmacological blockade of NAc dopamine receptors blocked corticosterone-induced potentiation of reinstatement. Intra-accumbens administration of corticosterone reproduced the behavioral effects of stress and systemic corticosterone. Corticosterone treatment acutely decreased NAc dopamine clearance measured by fast-scan cyclic voltammetry, suggesting that inhibition of uptake2-mediated dopamine clearance may underlie corticosterone effects. Consistent with this hypothesis, intra-accumbens administration of the uptake2 inhibitor normetanephrine potentiated cocaine-induced reinstatement. Expression of organic cation transporter 3, a corticosterone-sensitive uptake2 transporter, was detected on NAc neurons. These findings reveal a novel mechanism by which stress hormones can rapidly regulate dopamine signaling and contribute to the impact of stress on drug intake

Elementary science teachers’ integration of engineering design into science instruction: results from a randomised controlled trial

This randomised controlled trial used a mixed-methods approach to investigate the frequency and how elementary teachers integrated engineering design (ED) principles into their science instruction following professional development (PD). The ED components of the PD were aligned with Cunningham and Carlsen’s [(2014). Teaching engineering practices. Journal of Science Teacher Education, 25, 197–210] guidelines for ED PD and promoted inclusion of ED within science teaching. The treatment group included 219 teachers from 83 schools. Participants in the control group included 145 teachers from 60 schools in a mid-Atlantic state. Data sources, including lesson overviews and videotaped classroom observations, were analysed quantitatively to determine the frequency of ED integration and qualitatively to describe how teachers incorporated ED into instruction after attending the PD. Results indicated more participants who attended the PD (55%) incorporated ED into instruction compared with the control participants (24%), χ2(1, n = 401) = 33.225, p \u3c .001,  = 0.308. Treatment and control teachers taught similar science content (p’s \u3e .05) through ED lessons. In ED lessons, students typically conducted research and created and tested initial designs. The results suggest the PD supported teachers in implementing ED into their science instruction and support the efficacy of using Cunningham and Carlsen’s (2014) guidelines to inform ED PD design

Trace Metal Exposure is Associated with Increased Exhaled Nitric Oxide in Asthmatic Children

Background Children with asthma experience increased susceptibility to airborne pollutants. Exposure to traffic and industrial activity have been positively associated with exacerbation of symptoms as well as emergency room visits and hospitalisations. The effect of trace metals contained in fine particulate matter (aerodynamic diameter 2.5 μm and lower, PM2.5) on acute health effects amongst asthmatic children has not been well investigated. The objective of this panel study in asthmatic children was to determine the association between personal daily exposure to ambient trace metals and airway inflammation, as measured by fractional exhaled nitric oxide (FeNO). Methods Daily concentrations of trace metals contained on PM2.5 were determined from personal samples (n = 217) collected from 70 asthmatic school aged children in Montreal, Canada, over ten consecutive days. FeNO was measured daily using standard techniques. Results A positive association was found between FeNO and children’s exposure to an indicator of vehicular non-tailpipe emissions (8.9 % increase for an increase in the interquartile range (IQR) in barium, 95 % confidence interval (CI): 2.8, 15.4) as well as exposure to an indicator of industrial emissions (7.6 % increase per IQR increase in vanadium, 95 % CI: 0.1, 15.8). Elevated FeNO was also suggested for other metals on the day after the exposure: 10.3 % increase per IQR increase in aluminium (95 % CI: 4.2, 16.6) and 7.5 % increase per IQR increase in iron (95 % CI: 1.5, 13.9) at a 1-day lag period. Conclusions Exposures to ambient PM2.5 containing trace metals that are markers of traffic and industrial-derived emissions were associated in asthmatic children with an enhanced FeNO response

Genomic regions associated with kyphosis in swine

<p>Abstract</p> <p>Background</p> <p>A back curvature defect similar to kyphosis in humans has been observed in swine herds. The defect ranges from mild to severe curvature of the thoracic vertebrate in split carcasses and has an estimated heritability of 0.3. The objective of this study was to identify genomic regions that affect this trait.</p> <p>Results</p> <p>Single nucleotide polymorphism (SNP) associations performed with 198 SNPs and microsatellite markers in a Duroc-Landrace-Yorkshire resource population (U.S. Meat Animal Research Center, USMARC resource population) of swine provided regions of association with this trait on 15 chromosomes. Positional candidate genes, especially those involved in human skeletal development pathways, were selected for SNP identification. SNPs in 16 candidate genes were genotyped in an F2 population (n = 371) and the USMARC resource herd (n = 1,257) with kyphosis scores. SNPs in <it>KCNN2 </it>on SSC2, <it>RYR1 </it>and <it>PLOD1 </it>on SSC6 and <it>MYST4 </it>on SSC14 were significantly associated with kyphosis in the resource population of swine (<it>P </it>≤ 0.05). SNPs in <it>CER1 </it>and <it>CDH7 </it>on SSC1, <it>PSMA5 </it>on SSC4, <it>HOXC6 </it>and <it>HOXC8 </it>on SSC5, <it>ADAMTS18 </it>on SSC6 and <it>SOX9 </it>on SSC12 were significantly associated with the kyphosis trait in the F2 population of swine (<it>P </it>≤ 0.05).</p> <p>Conclusions</p> <p>These data suggest that this kyphosis trait may be affected by several loci and that these may differ by population. Carcass value could be improved by effectively removing this undesirable trait from pig populations.</p

Is the pharmacy profession innovative enough?: meeting the needs of Australian residents with chronic conditions and their carers using the nominal group technique

Background Community pharmacies are ideally located as a source of support for people with chronic conditions. Yet, we have limited insight into what innovative pharmacy services would support this consumer group to manage their condition/s. The aim of this study was to identify what innovations people with chronic conditions and their carers want from their ideal community pharmacy, and compare with what pharmacists and pharmacy support staff think consumers want. Methods We elicited ideas using the nominal group technique. Participants included people with chronic conditions, unpaid carers, pharmacists and pharmacy support staff, in four regions of Australia. Themes were identified via thematic analysis using the constant comparison method. Results Fifteen consumer/carer, four pharmacist and two pharmacy support staff groups were conducted. Two overarching themes were identified: extended scope of practice for the pharmacist and new or improved pharmacy services. The most innovative role for Australian pharmacists was medication continuance, within a limited time-frame. Consumers and carers wanted improved access to pharmacists, but this did not necessarily align with a faster or automated dispensing service. Other ideas included streamlined access to prescriptions via medication reminders, electronic prescriptions and a chronic illness card. Conclusions This study provides further support for extending the pharmacist’s role in medication continuance, particularly as it represents the consumer’s voice. How this is done, or the methods used, needs to optimise patient safety. A range of innovative strategies were proposed and Australian community pharmacies should advocate for and implement innovative approaches to improve access and ensure continuity of care