Notes

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Opioid use disorder (OUD) is a significant health problem, and understanding mechanisms of various aspects of OUD including drug use and withdrawal is important. Preclinical models provide an ideal opportunity to evaluate mechanisms underlying opioid withdrawal. Current models are limited by their reliance upon forced opioid administration, focus on the acute (and not protracted) syndrome, and exclusion of women. In this study, male and female rats self-administered heroin (maintenance dose of 12.5 μg/kg/infusion) opioid withdrawal after abrupt discontinuation was measured. In Phase 1, acute withdrawal symptoms were rated in male and female rats at 0, 16, 48, and 72 hr after the last self-administration session. Total somatic signs increased until 48 hr (predominantly in women), and heroin intake positively correlated with total somatic signs at the 48 and 72 hr timepoints. Measures of hyperactivity and anxiety-like behavior increased by 16 and 48 hr, respectively. In Phase 2, symptoms were assessed at baseline, acute, and protracted (168 and 312 hr after self-administration) timepoints in a subset of male and female rats from Phase 1. The total number of somatic signs did not differ across timepoints, though women displayed significantly higher body temperature at all timepoints compared with men, indicating sex-specific protracted withdrawal symptomatology. These data provide a thorough characterization of rodent opioid withdrawal symptomatology after self-administration and abrupt discontinuation that serve as a foundation for future studies designed to mimic the human experience, and demonstrate the importance of characterizing acute and protracted withdrawal with sex-specificity in preclinical models of opioid self-administration. (PsycInfo Database Record (c) 2020 APA, all rights reserved).Attention-deficit/hyperactivity disorder is associated with impaired cognitive functioning and increased delay discounting (i.e., a stronger preference for immediate reward). At the group level, stimulant medication improves cognition and delay discounting, yet not all children exhibit problems in these domains, and previous work has not examined whether stimulant-induced improvements are moderated by baseline performance. To address this question in the current study, 82 children with attention-deficit/hyperactivity disorder (9-12 years old) attended a week-long research camp. On the baseline day (Monday), participants completed tasks of inhibitory control, visuospatial working memory, reaction time variability, and delay discounting. Children then completed a 3-day, randomized, double-blind, placebo-controlled trial of ∼1 mg/kg and 2 mg/kg long-acting methylphenidate (mean doses = 39.1 and 74.3 mg, respectively), during which they were readministered the battery of tasks. Cognitive composites (mean of inhibitory control, working memory, and reaction time variability performance) were created for the baseline and medication evaluation phases. As predicted, the extent to which cognition was improved with medication compared with placebo and with 2 mg/kg compared with 1 mg/kg was greatest among children with poorer baseline cognitive function. Children with stronger baseline cognition exhibited less improvement with methylphenidate compared with placebo and did not benefit from the 2 compared with the 1 mg/kg dose. In contrast, medication-related improvement in delay discounting was unrelated to baseline discounting. Given that improving cognitive function is one potential mechanisms by which stimulants exert their therapeutic effects, this study has significant implications for understanding how and for whom stimulant medication works. (PsycInfo Database Record (c) 2020 APA, all rights reserved).This study was designed to assess whether nicotine can acquire additional reinforcing properties through associations with other rewards. To this end, rats self-administered nicotine-alone (0.01 mg/kg) or nicotine paired with access to sucrose during the conditioning phase. In the subsequent challenge phase, we tested the effect of nicotine-sucrose pairings on the reinforcing effects of nicotine using a progressive ratio schedule of reinforcement. Using this approach, we show that (a) rats in both paired and nicotine-alone conditions self-administered similar amounts of nicotine in the initial conditioning phase of the study when intake was limited to 10 infusions per session, (b) nicotine rapidly acquired control over goal-tracking behavior in the paired condition, (c) rats that had a history of nicotine and sucrose pairings worked harder and took more nicotine as measured on a progressive ratio using a distinct response form, and (d) conditioned goal-tracking evoked by nicotine did not show extinction when sucrose was no longer paired with nicotine over the 11 days of nicotine self-administration on a progressive ratio schedule of reinforcement. Overall, our results demonstrate that in addition to the multifaceted nature of nicotine stimulus that includes primary reinforcing effects, conditioned reinforcing effects, and reward enhancing effects, nicotine can also acquire additional reinforcing properties through associations with other rewards. This ability to acquire additional reinforcing properties through associative learning may contribute to the development and perpetuation of tobacco use disorder. (PsycInfo Database Record (c) 2020 APA, all rights reserved).Opioid use disorder (OUD) is a national public health concern. Aurora Kinase inhibitor Craving, stress, and exposure to conditioned drug cues are implicated in risk of relapse to opioids. Although impaired sleep has been implicated in risk of relapse to other substances of misuse, little research to date has examined the relationship between sleep and craving in individuals with OUD. The present study examined sleep as a moderator of the relationship between craving and stress in a randomized controlled human laboratory study. Individuals with current OUD (N = 39) completed a 1-night hospital stay to control for factors that may affect craving, stress, and sleep. Sleep was monitored via an actigraphy watch and the Pittsburgh Sleep Quality Index. The next morning, participants were randomized to a 15-min laboratory stress task or a no-stress condition. All participants were then exposed to a 15-min opioid cue paradigm, and craving was measured via self-report. Moderation models were conducted to evaluate whether the sleep indices moderated the relationship between stress condition (independent variable) and craving (dependent variable). Average self-reported nightly sleep duration moderated the relationship between stress condition and craving for participants in the no-stress condition (b = 0.95, p less then .05). Specifically, participants in the no-stress condition with lower average nightly sleep duration exhibited significantly greater craving following the opioid cue paradigm. Although preliminary, the findings add to the literature on craving, stress, and sleep among individuals with OUD. Sleep impairment may be an important target of a comprehensive, long-term treatment plan for some patients with OUD. (PsycInfo Database Record (c) 2020 APA, all rights reserved).There has been a lack of research on the third area of impairment noted in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition-"occupational functioning." It is important to understand the impact of common treatments for attention-deficit/hyperactivity disorder (ADHD) in occupational settings. Twenty individuals with ADHD between ages 16 and 25 participated in a double-blind, placebo controlled evaluation of 40 mg lisdexamfetamine dimesylate in a setting designed to approximate a restaurant workplace with associated, simulated food delivery. Outcome measures included ratings of performance, as well as behavioral productivity. Results indicated that participants completed more workplace tasks when on medication, relative to placebo. Ratings of job application quality, job interview performance, and delivery outcomes were not significantly different on medication versus placebo. These results suggest positive effects of medication in a workplace environment, but also a need for study of additional interventions to support workplace-related behavior and functioning. (PsycInfo Database Record (c) 2020 APA, all rights reserved). TRIAL REGISTRATION ClinicalTrials.gov NCT03446885.E-cigarettes are popular among adolescents. Given that flavors enhance e-cigarette appeal, this study examined the influence of flavors on nicotine in e-cigarettes. Youth e-cigarette users (average 26.2 days [SD = 3.6] in past 28 days) were randomized to use e-cigarettes containing 6 or 12 mg/mL of freebase nicotine and completed 4 test sessions. During the first 3 test sessions, participants completed 3 fixed puffing bouts (1 puffing bout = 10 puffs, 3 s each, 30-s interval), using menthol, green-apple, and unflavored e-liquids (50 propylene glycol [PG]/50 vegetable glycerin [VG]) with their assigned nicotine concentration in a random order using a ∼5.5-W V2 e-cigarette device. After each puffing bout, participants assessed subjective effects of nicotine and flavor. In the 4th test session, participants used any of the e-liquids they had tried in the earlier sessions, ad libitum for 60 min and the amount of e-liquid used for each flavor and the number of puffs was assessed. Participants (n = 49; 6 mg/mL [n = 24]; 12 mg/mL [n = 25]) were 63.3% male, 65.3% non-Hispanic White with an average age of 18.7 (SD = 0.9). Mixed models analysis revealed that green apple and 6 mg/mL of nicotine independently increased liking of e-cigarette taste. In addition, green apple produced higher ratings of fruitiness, sourness, sweetness, and menthol produced higher ratings of coolness. We did not observe any interactions between nicotine and flavor. Youth liked the taste of e-liquids containing green-apple flavor or low nicotine concentration which highlights the appeal of fruit flavors in e-cigarettes to adolescents. (PsycInfo Database Record (c) 2020 APA, all rights reserved). TRIAL REGISTRATION ClinicalTrials.gov NCT03168191.Preclinical studies of nicotine self-administration provide important value for the field as they are highly rigorous, controlled, can be conducted quickly, and are generalizable to humans. Given the translational value of the nicotine self-administration model, and the relatively new guidelines of the National Institutes of Health to include sex as a biological variable, strain and sex differences in nicotine acquisition were examined here in two outbred rat strains. Sprague-Dawley (SD) and Long-Evans (LE; wildtype and cholinergic acetyltransferase cre-recombinase transgenic) rats of each sex were implanted with indwelling intravenous jugular catheters. Rats were trained to self-administer nicotine (0.02 mg/kg per infusion, paired with contingent light + tone stimuli). Acquisition criteria were set at a minimum activeinactive response ratio of 21 and a minimum of 10 infusions per session, both of which had to be met for a minimum of 10 sessions. Across 10 sessions, male SD rats self-administered significantly more nicotine than female SD rats (p less then .05), indicating a sex difference in this strain. LE females self-administered more nicotine than SD females indicative of a strain difference between females (p less then .05). SD males increased nicotine infusions across sessions compared to LE males and SD females (p less then .05). No strain or sex differences were observed in the number of sessions to reach criteria. No differences between wildtype and transgenic LE rats were observed. These results demonstrate sex and strain differences in nicotine self-administration between SD and LE rats and may lend insight into development of other nicotine self-administration models, where sex and strain may impact acquisition. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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